Publication for TLR7 and TLR8

Species Symbol Function* Entrez Gene ID* Other ID Gene
coexpression		 CoexViewer
hsa TLR7 toll like receptor 7 51284 [link]
hsa TLR8 toll like receptor 8 51311

Pubmed ID Priority Text
26134824 0.98 TLR7 or TLR8 in pancreatic cells from patients with chronic pancreatitis and pancreatic cancer, compared to no, or occasionally low expression in normal pancreatic tissue (Fig. 1B).
0.98 TLR7 and TLR8 expression in mediating inflammation in pancreatic cancer cells we first examined in the present study their expression in human tissues from primary pancreatic cancers.
0.97 TLR7 and TLR8 expression in PANC1 cancer cells on chemosensitivity transduced tumor cells were treated with two different concentrations of 5-FU (100 and 1000 mumol/l) as approximated concentrations for LD50.
0.97 TLR7+ and TLR8+ cells, 49 and 56% vs. 46% in empty vector cells (Fig. 8B; P<0.05 and P<0.0001).
0.97 TLR7 and TLR8 were indeed cancer cells.
0.97 TLR7+ and TLR8+ PANC1 cells without (**P<0.002 and **P<0.005) and with R848 stimulation (***P<0.02 and *P<0.0001) compared to empty vector PANC1 cells analyzed by MTS assay.
0.97 TLR7+ and TLR8+ PANC1 cells.
0.96 TLR7/TLR8 signaling leading to tumor cell proliferation and chemoresistance.
0.96 TLR7 and TLR8 in pancreatic cancer cells results in increased tumor cell proliferation and reduced chemosensitivity.
0.96 TLR7 and TLR8.
0.95 TLR7/TLR8 expression increased tumor growth in vivo.
0.95 TLR7 and TLR8 expressing cancer cells, we dissected the expression of COX-2 in the pancreatic tumor cells by immunohistochemical staining and western blot analysis.
0.95 TLR7 and TLR8 expression is upregulated in tumor cells of patients with colorectal cancer.
0.94 TLR7 and TLR8 causes increased proliferation in TLR7+ and TLR8+ PANC1 cells.
0.93 TLR7 and TLR8 expression is associated with tumor progression in patients with colorectal cancer and reduced tumor-specific survival among patients with high TLR7 and TLR8 expression in their cancer cells.
0.93 TLR7 and TLR8.
0.93 TLR7 and TLR8 expressing pancreatic cancer cells.
0.93 TLR7 and/or TLR8 ligands.
0.93 TLR7 and TLR8 were also found in pancreatic cells from chronic pancreatitis while CD34 was not or sporadic detectable (arrows).
0.92 TLR7 and TLR8 seems to stimulate the expression of Notch-2 receptor.
0.92 TLR7 and TLR8.
0.92 TLR7 and TLR8 protein expression in transduced PANC1 cells by western blot analysis.
0.92 TLR7+ and TLR8+ PANC1 (*P<0.0001 and **P<0.0005) cells compared to empty vector PANC1 cells.
0.92 TLR7+ PANC1 cells (***P<0.05) and TLR8+ PANC1 cells (*P<0.0001) to different concentrations of 5-FU compared to empty vector PANC1 cells analyzed by MTS assay.
0.91 TLR7+ and TLR8+ PANC1 cells with R848 resulted in significantly increased gene expression levels of NF-kappaB (*P<0.0001) 6 h post stimulation.
0.90 TLR7 and TLR8 we generated TLR7 and TLR8 expressing human PANC1 cancer cells and analyzed the effects of TLR7/8 agonists (R848, resiquimod) in the inflammatory process on tumor cell proliferation and chemoresistance.
0.90 TLR7 and TLR8 expression of pancreatic cancer cells.
0.89 TLR7+ and TLR8+ PANC1 cancer cells 5-fluorouracil was used.
0.88 TLR7/TLR8 in UICC stage I-IV pancreatic cancer, chronic pancreatitis, normal pancreatic tissue and human pancreatic (PANC1) cancer cell line was examined.
0.87 TLR7+ PANC1 cells and TLR8+ PANC1 cells compared to empty vector PANC1 cells (*P<0.0001) found by MTS assay.
0.86 TLR7, TLR8 and CD34 were demonstrated.
0.84 TLR7 and TLR8 expression and signaling in tumor cell proliferation and chemoresistance in pancreatic cancer.
0.84 TLR7 or TLR8 stimulation increased tumor cell survival and resistance to the chemotherapeutic substance 5-fluorouracil.
0.82 TLR7 or TLR8 expression was detected in normal pancreatic cells (Fig. 1A), an observation that we believe to be novel.
0.82 TLR7 blue line, TLR8 red line, CD34 purple line and IgG control black line.
0.81 TLR7/TLR8 overexpressing PANC1 cell lines were generated and analyzed for effects of (un-)stimulated TLR expression on tumor cell proliferation and chemoresistance.
0.79 TLR7 or TLR8 by transduced PANC1 cells was demonstrated by western blot analysis.
0.78 TLR7 expression of pancreatic cells in all analyzed subjects with pancreatic cancer and with chronic pancreatitis was more intense than TLR8.
0.78 TLR7 and TLR8 transduced human PANC1 cancer cells in Balb/c nude mice was examined.
0.78 TLR7+ and TLR8+ PANC1 cancer cells compared with untreated cells (Fig. 7A and B; P<0.0001).
0.78 TLR7+ and TLR8+ PANC1 cancer cells.
0.77 TLR7 and TLR8 expression, known to be associated with single stranded RNA (virus) infection in this context may be associated with recognition of pathogenic viruses in the investigated human pancreatic cancers remains speculative.
0.76 TLR7 and TLR8 expressing cancer cells.
0.76 TLR7+ and TLR8+ PANC1 cancer cells was demonstrated when compared to empty vector PANC1 cells, pointing to an increased chemoresistance in the cells.
0.76 TLR7, TLR8 and CD34 was detected (arrows) in pancreatic cancer cells (UICC III).
0.76 TLR7 (Cy3 red and DAPI blue for nuclear counterstaining) and TLR8 (Cy3 red and DAPI blue for nuclear counterstaining) (arrows).
0.71 TLR7 and TLR8.
0.71 TLR7 and CD34 was detected in normal pancreatic cells, little expression of TLR8 was observed (arrow).
0.71 TLR7+ PANC1 cells at 12 h (**P<0.005, ***P<0.05) and for TLR8+ PANC1 cells at 24 h (*P<0.0001, **P<0.005, ***P<0.05).
0.67 TLR7 and TLR8 stimulation an upregulation of several genes involved in angiogenesis as well as proinflammatory cytokines such as IL-8 and IL-12.
0.65 TLR7 and TLR8 expression in the cancer cells.
0.64 TLR7 and TLR8 signaling pathways in TLR7+ and TLR8+ expressing pancreatic cancer cells may have the potential to sustain cancer progression.
0.63 TLR7 or TLR8 stimulation of human PANC1 cells induces gene expression of NF-kappaB and COX-2
0.61 TLR7 and TLR8 expression in pancreatic cancer.
0.60 TLR7 and TLR8 in several purchased human pancreatic cancer cell lines.
0.60 TLR7 and TLR8 stimulation with the agonist R848 further increases proliferation of TLR7+ and TLR8+ PANC1 cancer cells.
0.59 TLR7 and TLR8 positivity in pancreatic cancer cells was detected (Fig. 4A, top and below right, and B, respectively).
0.55 TLR7 and TLR8 protein expression in pancreatic cancer (UICC III) compared to normal pancreatic tissue by western blot analysis.
0.53 TLR7 and TLR8 was detected in chronic pancreatitis.
0.52 TLR7 and TLR8 was observed in the transduced PANC1 cells (TLR7+ and TLR8+ PANC1 cells) by qRT-PCR and following agarose gel electrophoresis (Fig. 5A and B).
0.52 TLR7 and TLR8 expression and the activation of Notch.
0.52 TLR7 and TLR8 in PANC 1 cells.
0.50 TLR7 and TLR8 expression increases tumor cell proliferation and promotes chemoresistance in human pancreatic cancer
22022576 0.98 TLR7 and TLR8 SNPs in the resolution of HCV-infection would require a comparison of patients who are chronically infected with HCV with individuals that have spontaneously cleared infections.
0.97 TLR7 and TLR8 and cytokine production induced ex vivo by TLR7- and TLR8-specific agonists using whole blood of subjects with different genotypes.
0.97 TLR7 IVS2-151A/TLR8 -129G (AG) was significantly lower in chronic HCV infection patients than control subjects (65.3% versus 83.2%; p<0.001).
0.97 TLR7 and TLR8 protein expression in monocytes of health male subjects with different genotypes of TLR7 and TLR8.
0.97 TLR7 IVS2-151G>A (rs179009) and TLR8-129G>C (rs3764879) allelic frequencies in other populations are shown in Table 3.
0.97 TLR7 and TLR8 are PRRs of interest in the setting of HCV-infection as they can bind ssRNAs and lead to the production of large amounts of the antiviral cytokine interferon-alpha by dendritic cells.
0.97 TLR7 and TLR8 might influence the immune response against HCV.
0.97 TLR7 and TLR8 variants have functional relevance in the setting of HCV-infection by conferring susceptibility to infection.
0.96 TLR7 and TLR8 played a significant role in anti-HCV immune responses.
0.96 TLR7 and TLR8 was significantly lower, but higher in intensity compared to cells from those with GG and AC haplotypes.
0.96 TLR7 and TLR8 had higher susceptibility to chronic HCV infection than those with wild type alleles.
0.96 TLR7 and TLR8 expression studies
0.96 TLR7 and TLR8 mRNA expression of individuals with different genotype by RT-PCR.
0.96 TLR7 IVS2-151A/TLR8 -129G genotype, represent individuals with TLR7 IVS2-151G/TLR8 -129G genotype and represent those with TLR7 IVS2-151A/TLR8 -129C genotype.
0.96 TLR7 and TLR8 expressions were significantly higher in cells from subjects with the AG haplotype compared to cells from those with the GG and AC haplotypes (Figure 2B & 2D).
0.96 TLR7 IVS2-151A/TLR8 -129G genotype, represent individuals with TLR7 IVS2-151G/TLR8 -129G genotype and represent those with TLR7 IVS2-151A/TLR8 -129C genotype.
0.96 TLR7 agonist (3M-001) (A-E) or TLR8 agonist (3M-002) (F-J) for 12 hr.
0.96 TLR7 (IVS2-151A>G) and TLR8 (-129G>C) polymorphisms also altered these gene expressions when quantified by mRNA.
0.96 TLR7 and TLR8 polymorphisms resulted in significantly different production of IFN-alpha, IL-1ss and IL-6 after stimulation with a TLR7 agonist, whereas only IL-1ss and TNF-alpha production were altered after stimulation with a TLR8 agonist (Figure 3).
0.96 TLR7 and TLR8 genes may impair the immune responses to HCV due to less IFN-alpha production during stimulation.
0.96 TLR7 and TLR8 variants result in reduced IFN-alpha release.
0.95 TLR7 and TLR8 genes might impair immune responses during HCV infection.
0.95 TLR7 and TLR8 protein expressions in monocytes of different genotypes from health male subjects were assessed by FACS.
0.95 TLR7 or TLR8 antibodies.
0.95 TLR7 expression represented as percentage of CD14-positive cells; (B) TLR7 expression represented as MFI; (C) TLR8 expression represented as percentage of CD14-positive cells; (D) TLR8 expression represented as MFI.
0.95 TLR7-specific agonist (3M-001) or a TLR8-specific agonist (3M-002) for 12 hours, after which the supernatants collected for cytokines assays.
0.95 TLR7 but not TLR8, are the primary producers of IFN-alpha.
0.95 TLR7 IVS2-151A/TLR8 -129G haplotype had higher induced interferon production and lower amounts of inflammatory cytokines than those with the GG and AC haplotypes after ex vivo whole blood stimulation with TLR7 and TLR8 agonists.
0.94 TLR7 IVS2-151A/TLR8 -129C (AC) haplotype had higher TLR7 and TLR8 mRNA expressions.
0.94 TLR7- and TLR8-specific agonists for whole blood ex vivo stimulation.
0.93 TLR7 and TLR8 genes are located on the X-chromosome, gender-specific effects come as no surprise.
0.91 TLR7 and TLR8, which share a high degree of structural similarity, are located in the membranes of the endosomal compartment and recognize viral single-stranded RNA (ssRNA).
0.91 TLR7 and TLR8 SNPs of 264 patients with chronic HCV infection and 243 control subjects were analyzed.
0.91 TLR7 and TLR8 mRNA expressions in healthy male volunteers with different TLR7 and TLR8 haplotypes.
0.90 TLR7 IVS2-151A/TLR8 -129C (AC) and TLR7 IVS2-151G/TLR8 -129G (GG) increased the risk for chronic HCV infection compared to wild type TLR7 IVS2-151A/TLR8 -129G (AG), with OR = 2.67 (95% CI = 1.36 to 5.22; p = 0.003) and OR = 2.49 (95% CI = 1.43 to 4.34; p = 0.001), respectively (Table 2).
0.88 TLR7 is expressed by plasmacytoid DCs and B cells, whereas TLR8 is abundant on monocytes and monocyte-derived DCs.
0.84 TLR7 (A) and TLR8 (B) mRNA was reverse transcribed and obtained by using the 2(-DeltaDeltaCT) method which was normalized with an endogenous control, glyceraldehydes-3 phosphate dehydrogenase (GAPDH).
0.84 TLR7 IVS2-151G>A and TLR8-129G>C polymorphisms were: 413 had the A allele (15.0%), 73 had the G allele (85.0%), and 46 had the C allele (9.5%), and 440 had the G allele (90.5%), respectively.
0.83 TLR7 and TLR8 gene polymorphisms.
0.82 TLR7 or TLR8 agonist stimulation during whole blood culture.
0.82 TLR7 IVS2-151A/TLR8 -129G genotype, represent individuals with TLR7 IVS2-151G/TLR8 -129G genotype and represent those with TLR7 IVS2-151A/TLR8 -129C genotype.
0.81 TLR7 and TLR8 protein expressions in monocytes from 37 healthy male subjects with different TLR7 and TLR8 genotypes: AG haplotype, N = 17; GG haplotype, N = 9; AC haplotype, N = 11.
0.63 TLR7 and TLR8 Gene Variations and Susceptibility to Hepatitis C Virus Infection
0.63 TLR7 IVS2-151A/TLR8 -129G haplotype against HCV chronic infection.
0.59 TLR7 allele frequencies were A at 77%, and G at 22%, and TLR8 allele frequencies were C at 16%, and G at 83%.
0.58 TLR7 and TLR8 in the immune response against HCV, a single-stranded RNA virus, is conceivable, as an antiviral effect of TLR7 stimulation has been demonstrated in early clinical studies.
22730373 0.98 TLR8 but not TLR7 was induced by LPS and IL-1beta stimulation in RA monocytes and macrophages.
0.98 TLR7 and TLR8 expression is increased in RA synovial tissue (ST) lining and sublining macrophages compared to normal (NL) ST
0.98 TLR7, anti-TLR8 and anti-CD68 antibodies in order to distinguish TLR7 and TLR8 staining on RA ST lining and sublining macrophages (original magnification x 400).
0.97 TLR7, TLR8 was undetectable in RA and NL fibroblasts.
0.97 TLR7 and TLR8 expression, NL PB monocyte differentiation to macrophages reduced the frequency of TLR2 positive cells, while the percentage of TLR4 positive cells was unchanged in these cell types.
0.97 TLR7 modulates TNF-alpha levels through an overlapping pathway and it further points out that although ssRNA is a potential ligand for both TLR7 and TLR8, TLR7 is the main sensor for ssRNA endogenous ligands in RA SF.
0.97 TLR7 (A) or anti-human TLR8 (C) (original magnification x 200) and positive immunostaining was scored on a 0-5 scale (B and D).
0.97 TLR7 and TLR8 are upregulated in RA synovial fluid (SF) compared to RA and NL PB macrophages
0.96 TLR7 and TLR8 have similar expression patterns in RA blood and ST and that both receptors are modulated by IL-17 in RA differentiated macrophages.
0.96 TLR7/TLR8, imidazoquinoline resiquimod (R848) is recognized as a potent synthetic agonist of TLR7/TLR8.
0.96 TLR7 and TLR8 in RA PB macrophages compared to PB monocytes, RA SF macrophages express the highest levels of these receptors.
0.96 TLR7 or TLR8 expression compared to RA monocytes.
0.96 TLR7 and TLR8 ligation.
0.95 TLR7 (Fig. 2A), TLR8 was undetectable in RA and NL fibroblasts (CT>40 cycles), however similar to TLR7 (Fig. 2B) expression of TLR8 was highly elevated in RA SF macrophages compared to RA and NL macrophages (Fig. 2E).
0.95 TLR7 or TLR8 in RA joint SF.
0.95 TLR7+ (n=5-8) (C) or %CD14+TLR8+ (n=5-9) (F) in each cell population.
0.94 TLR8 expression in RA monocytes with DAS28, TLR7 or TNF-alpha levels (Fig. 5B, C, E).
0.94 TLR7 (C-D) or FITC labeled anti-CD14 antibody and Alexa 647-conjugated anti-TLR8 (F-G) in order to determine the percentage of CD14+ and TLR7/8 positive cells.
0.94 TLR7 and TLR8 ligation in RA monocytes and differentiated macrophages and R848-induced CCL2 production is modulated by PI3K, NF-kappaB pathways in RA differentiated macrophages
0.93 TLR7/ TLR8 are elevated in RA ST lining and sublining macrophages compared to normal ST.
0.93 TLR8 positive RA monocytes and macrophages (95% and 75%) were comparable to TLR7 positive cells (75% and 55%) (Figs. 2C-D and 2F-G).
0.93 TLR7 but not TLR8 expression correlates with DAS28 and TNF-alpha levels in RA monocytes
0.92 TLR7 and TLR8 are significantly higher in RA monocytes compared to macrophages and ligation of a TLR7/8 agonist induces TNF-alpha production, we next asked whether mRNA levels of TLR7 and TLR8 in RA monocytes correlate with DAS28, TNF-alpha levels or each other.
0.92 TLR7 but not TLR8 have a linear correlation with DAS28 and TNF-alpha levels.
0.92 TLR7 and TLR8 is modulated by IL-17 and therefore there may be a positive feed back loop between ligation of TLR7 and TLR8 and polarization of TH-17 cells.
0.91 TLR7 and TLR8 expression levels (Figs. 3A, C) while TLR7 expression was unresponsive to stimulation in RA monocytes (Fig. S2).
0.89 TLR7 or TLR8 mRNA levels were determined in NL (n for monocytes or macrophages=11 or 18) and RA PB monocytes (n=11) and differentiated macrophages (n=15) as well as in RA SF macrophages (n=10) by employing real-time RT-PCR.
0.88 TLR7 and TLR8 immunostaining was markedly higher in ST lining and sublining macrophages compared to normal ST (Figs. 1A-D).
0.87 TLR7 and TLR8 in RA, OA, and NL joints, STs were stained with antibodies specific for these receptors.
0.86 TLR7 and TLR8 expression was greatly elevated in RA monocytes compared to RA macrophages, ligation of these receptors with a higher dose of R848 (1 microg/ml) resulted in similar production levels of TNF-alpha and CCL2 in both cell types (Figs 3F, 4C).
0.83 TLR7 and TLR8 in rheumatoid arthritis (RA).
0.80 TLR7 and TLR8 was demonstrated in RA, osteoarthritis (OA) and normal (NL) synovial tissues (ST) employing immunohistochemistry.
0.79 TLR7 was determined in RA macrophages (A) as well as expression levels of TLR8 in RA monocytes (B) and differentiated macrophages (C) were measured by real-time RT-PCR (n=5-10).
0.77 TLR7 and TLR8 having similar pattern of expression in RA ST and PB cells, mRNA expression of these receptors does not correlate in RA monocytes or macrophages and as a result only TLR7 expression correlates with higher disease activity and TNF-alpha transcription in the RA joint.
0.75 TLR7 but not TLR8 correlates with DAS28 score and TNF-alpha levels
0.69 TLR7/TLR8 are greatly elevated in RA SF macrophages and PB monocytes compared to their normal counterparts.
0.69 TLR7 and TLR8-induced CCL2 production, in RA macrophages, cells were untreated (DMSO) or treated with 10 microM inhibitors to p38 (SB203580), ERK (PD98059), PI3K (LY294002) or NF-kappaB (MG-132) for 1h.
0.66 TLR8 in these cells does not correlate with DAS28, TLR7 or TNF-alpha levels.
0.59 TLR8 is not expressed in RA fibroblasts but has a similar expression pattern to TLR7 in RA SF and PB differentiated macrophages
28122964 0.98 TLR7/8 was supported by the observation that the monocyte to macrophage differentiation by HCV was blocked by TLR7 or TLR8 knock-down and not by TLR3 knockdown in monocytes, indicating that TLR7/8 mediates the effect of HCV.
0.97 TLR7 and TLR8 expression is increased in circulating monocytes with high collagen levels in HCV-infected patients
0.97 TLR7 or TLR8 and co-cultured with HCV or Huh concentrate.
0.97 TLR7 knockdown partially and TLR8 knockdown completely abrogated the expression of collagen in the monocytes which were exposed to HCV (Fig 6D).
0.96 TLR7 or TLR8 could prevent the effect of HCV on monocyte differentiation.
0.96 TLR7 and TLR8 expression did not correlate with fibrocyte levels in chronic HCV patients (Fig 6F).
0.96 TLR7/8 agonist we conclude that the mixed M1/M2 phenotype may be due to activation of TLR7 and TLR8 by HCV.
0.95 TLR7 and TLR8 or as a dsRNA via TLR3 or RIG-I. Monocytes were treated with Lyovec (control), Poly I:C (TLR3 ligand), Gardiquimod (TLR7), ssRNA40/Lyovec (TLR8 ligand) or PolyI:C/Lyovec (RIG-I ligand) for 7 days to assess the effect of direct PAMP stimulation on monocyte differentiation.
0.90 TLR7 and TLR8.
0.89 TLR7 and TLR8 in HCV mediated monocyte differentiation.
0.88 TLR7 or TLR8 agonist, Gardiquimod or ssRNA40 induced monocyte differentiation to MPhis.
0.85 TLR7 and TLR8 were determined by PCR.
0.83 TLR7/TLR8 in chronic HCV-infection in generation of polarized macrophages as well as fibrocytes.
0.82 TLR7 or TLR8 stimulation, independent of HCV, caused monocyte differentiation and M2-MPhi polarization.
0.82 TLR7 and TLR8 in induction of fibrocytes in HCV-infection.
0.79 TLR7 siRNA transfection led to partial but significant reduction in the cytokine secretion as compared to TLR8 knockdown (Fig 4C, D).
0.77 TLR8, and not TLR3 or TLR7, siRNA transfection decreased the expression of CD68 and CD206 (Fig 4B).
0.70 TLR7 and TLR8 levels in monocytes and also high expression of pro-collagen.
0.66 TLR7 and TLR8 levels and to a lesser extent of TLR3 in HCV patient monocytes as compared to that of healthy controls (Fig 6A-C).
0.61 TLR7 and TLR8 in circulating monocytes that was associated with increased intracellular expression of pro-collagen.
0.57 TLR7/TLR8 ligands independent of HCV can program monocytes to differentiate into M2 polarized macrophages with features of fibrocytes.
0.54 TLR7 or TLR8 is associated with inhibition of collagen expression in HCV-exposed monocytes.
0.53 TLR7 and TLR8 activation with Gardiquimod and ssRNA40/Lyovec, respectively, increased the expression of CD14 and CD68 on monocytes along with M2 markers, CD206 and CD163 (Fig 3A, B).
0.52 TLR8 completely, and of TLR7 partially attenuated collagen expression in monocytes exposed to HCV suggesting the role of TLR8 and TLR7 in induction of fibrocytes in HCV-infection.
0.51 TLR7 and TLR8.
0.50 TLR7- or TLR8-specific siRNA, respectively, knocked-down their expression in monocytes (Supplementary Fig 3).
31501466 0.98 TLR7 gene, as well as its neighboring paralog TLR8, was increased compared to healthy men.
0.98 TLR7 CN and TLR8 CN was seen within each sample from healthy men or healthy women (respectively, Spearman r = 0.40 and r = 0.50, P < 0.0001, Fig. 2).
0.98 TLR7 CN (mean: 1.05 +- 0.11 copies) and TLR8 CN (mean 1.09 +- 0.21 copies) in blood DNA samples compared to healthy men (respectively, 0.97 +- 0.07 copies, P < 0.0001 and 0.97 +- 0.08 copies, P < 0.0001, Fig. 3).
0.98 TLR7 and >= 1.13 for TLR8 CN), thus, high CN is associated with a confidence level of >=97.72%.
0.97 TLR7 and TLR8 genes are phylogenetically related as they are paralogs.
0.97 TLR7 and TLR8 gene copy numbers (CN) were calculated by comparison with the mean of two reference genes, as detailed in the method section, on peripheral blood DNA samples from 172 healthy men and 179 healthy women.
0.97 TLR7 and TLR8 (mean +- standard deviation: 0.97 +- 0.07 and 0.97 +- 0.08 copies, respectively) and healthy women had ~2 copies of TLR7 or TLR8 (respectively, 1.86 +- 0.12 and 1.83 +- 0.15 copies).
0.97 TLR7 and TLR8 genes was defined as having a z-score >=2, i.e. being superior or equal to the mean value observed in HM plus two standard deviations (>=1.11 for TLR7 CN and >=1.13 for TLR8 CN represented by the blue dot line).
0.97 TLR7 and TLR8 CN were similarly significantly increased in men with RA compared to healthy men when men from both groups were age-matched (Suppl.
0.97 TLR7 and TLR8 genes are increased in peripheral blood cells of men with RA compared to healthy men.
0.96 TLR7 and TLR8 influences TLR7/8 mRNA levels and mRNAs of proteins involved in TLR pathways.
0.96 TLR7: 1.01 copies +-0.04 and TLR8: 0.99 +- 0.06, data not shown).
0.96 TLR7 and TLR8, e.g. Forkhead Box P3 (FOXP3), might have their expression affected by the XXY and XX mosaicism but were not tested in the present study due to limited availability of biological specimens.
0.95 TLR7 or TLR8 CN
0.93 TLR7 gene and its paralog TLR8.
0.88 TLR7 and TLR8 mRNA expression was not increased in men with high TLR7/8 CN as it would have been if TLR7/8 genes were duplicated and translocated on another chromosome, as described in the Yaa mouse model.
0.82 TLR7 and TLR8 genes in blood samples from men with RA.
0.81 TLR7 and TLR8 CN assessment method on healthy controls
0.81 TLR7 and TLR8 gene copy numbers (CN) were calculated as detailed in the method section on peripheral blood DNA samples from 64 men with RA (RA) compared to 171 healthy men (HM).
0.75 TLR7 and TLR8 genes.
0.73 TLR7 CN (group B) did not show higher TLR7 or TLR8 mRNA expression relative to patients with normal TLR7 CN (group A).
0.69 TLR7 and its neighboring paralog TLR8 (or the genetic region containing them) are at increased CN in peripheral blood of RA men compared to healthy men.
0.68 TLR7 and TLR8 CN did not increase with age in either DNA samples from peripheral blood of healthy men from birth to 74 years old or healthy women from birth to 82 years old (Fig. 4).
0.56 TLR7 and TLR8 are located in endosomal compartments and both recognize single-stranded RNA.
0.55 TLR7 and TLR8 CN (Fig. 1).
25785446 0.98 TLR7 or TLR8 activation only limited ORN sequences are available.
0.98 TLR7 and TLR8 differ in their target cell selectivity and cytokine induction profile we hypothesized that RNA63 mediated IFN-alpha production is TLR7 dependent, whereas production of proinflammatory cytokines is mediated by human TLR8.
0.97 TLR7- or TLR8-specific imidazoquinolines have been used preclinically, however systemic application is generally not applicable due to strong side effects.
0.96 TLR7- and TLR8-mediated cytokine secretion.
0.95 TLR7 or TLR8 activation suggesting an important role of 2'-O-methylation for shaping differential TLR7 or TLR8 activation.
0.95 TLR7- / TLR8-activating RNA to a TLR8-specific ligand.
0.94 TLR7 or TLR8 activation.
0.91 TLR7 and TLR8 mediated immune stimulation.
0.87 TLR7/8 ligand RNA63 into a TLR8-specific activator
0.83 TLR7 / TLR8 activation.
0.82 TLR7 or TLR8.
0.79 TLR7 and TLR8 are activated by nucleoside analoga (e.g. imidazoquinolines such as imiquimod or resiquimod), poly-U or GU-rich single stranded (ss) oligoribonucleotides (ORN), viral RNA and siRNA.
0.63 TLR8 binding of CL097, a TLR7/8 activating imidazoquinoline, are available, structural information on RNA-binding by TLR7 and TLR8 will be necessary to fully understand the effect of 2'-O-methylation on TLR activation.
0.60 TLR8 but not TLR7.
0.60 TLR7 is only expressed in plasmacytoid dendritic cells and B cells, whereas TLR8 is found in monocytes, myeloid dendritic cells and regulatory T cells.
0.58 TLR7 and TLR8, their side effects potentially pose a problem for systemic application.
0.52 TLR7 / TLR8 ligand to an exclusively TLR8-specific ligand.
24892454 0.98 TLR7, TLR8 and TLR9 was determined for the monocyte populations of 13 patients diagnosed with HIV and 13 apparently healthy subjects used as controls.
0.98 TLR7, TLR8 and TLR9 expression in the monocyte population showed no significant differences between the patient and control groups (Table 2).
0.97 TLR7, TLR8 and TLR9 was determined in monocytes from HIV-infected patients (n= 13) and control subjects (n= 13), which were activated with specific ligands.
0.96 TLR7, TLR8 and TLR9 in peripheral blood monocytes from HIV-infected patients
0.96 TLR expression by RT-PCR in the monocyte population of apparently healthy individuals, observing high expression levels of TLR1, a moderate expression of TLR8, and a weak expression of TLR7 and TLR9.
0.95 TLR (TLR7, TLR8, and TLR9) in monocytes from HIV-infected patients, and it is unknown whether there are alterations in the signaling pathway used by these receptors.
0.95 TLR7, TLR8, and TLR9 with MyD88, and NF-kBp65, respectively, shows a significant negative correlation between the TLR8 and NF-kBp65.
0.94 TLR7, TLR8, TLR9) and surface location (TLR1, TLR2, TLR4, TLR5, TLR6, TLR10) .
0.93 TLR8 ligands and to a lesser extent to the TLR7 ligands.
0.92 TLR7, TLR8 and TLR9, and activation of its signaling pathway in monocytes from patients infected with HIV.
0.88 TLR7, TLR8, TLR9 and the activation of its signaling pathway in the peripheral blood monocyte population of patients infected with HIV by means of flow cytometry and may be considered a pilot study.
0.87 TLR7 and TLR8 are expressed on B cells and monocytes while DC plasmacytoids (DCps) express only TLR7 and immature DCs (DC11c+) express only TLR8.
0.85 TLR7, TLR8 and TLR9 expression in HIV infected patients is due to the low levels of VL as a result of ARVT being administered.
0.52 TLR in peripheral blood monocytes The PBMC (n= 13) of patients and control subjects (n= 13) were immune-stained for DC14, TLR7, TLR8, TLR9, and analyzed by flow cytometry, as described in material and methods section.
30972055 0.98 TLR8, not TLR7, in the endolysosomal compartment, the first description of the participation of TLR8 in the sensing of eukaryotic pathogens.
0.97 TLR8 but not TLR7 leading to IFN-gamma induction in NK cells.
0.97 TLR7 (A) and TLR8 (B) were transfected with an NF-kappaB-gLuc reporter plasmid and stimulated with 1 mug/mL of the small-molecule ligands CL264 and CL075 or with RNA as indicated.
0.97 TLR8 stimulation is known to induce high levels of TNF and IL-12p70 release, while TLR7 activation in human PBMC induces high levels of IFN-alpha.
0.97 TLR8 induced IFN-gamma from NK cells can be boosted by type-I IFN, particularly during simultaneous TLR7 and TLR8 activation.
0.96 TLR7 and TLR8.
0.96 TLR7 expression, and, in this setting, both TLR7 and TLR8 activation lead to TNF release.
0.95 TLR8 shares many common RNA and small-molecule ligands with TLR7, yet differential activators of TLR7 and TLR8 have been described, and recent studies utilizing CRISRPR/Cas9 genome editing in human cells have shown that human TLR8 can preferentially recognize bacterial RNA and initiate antibacterial host defense.
0.95 TLR8-/- or TLR7-/-TLR8-/- cell lines (Figure 2C).
0.94 TLR7-/-, TLR8 -/-, or TLR7-/- TLR8 -/- cells were primed with 200 U/mL IFN-gamma and stimulated with RNA (C) or P. falciparum-infected (iRBC) or uninfected (uRBC) red blood cells (D) as indicated.
0.93 TLR8-/- and TLR7-/-TLR8-/- but not TLR7-/- deficient cells (Figure 2D), thus demonstrating that iRBC are capable of TLR8 but not TLR7 activation.
0.92 TLR7/8 ligand 9.2s RNA was used as a positive control and induced TNF release in WT, TLR7-/-, TLR8-/- but not TLR7-/-TLR8-/- THP-1 cells.
0.87 TLR7 and TLR8 activation under endogenous, endosomal conditions, we also generated TLR7-deficient (TLR7-/-), TLR8-deficient (TLR8-/-), and double-deficient (TLR7-/-TLR8-/-) monocytic THP-1 cell lines using CRISPR/Cas9 genome editing technology (Supplementary Table 1).
0.84 TLR7 and TLR8, we utilized HEK293-XL cell lines (Invivogen) overexpressing human TLR7 or TLR8 (HEK-TLR7, HEK-TLR8).
24445780 0.98 TLR7, 1 in TLR8, 2 in TLR3) with SLE and with specific clinical manifestations of SLE.
0.97 TLR7 and TLR8 are on the X chromosome (Xp22.2) and play critical roles in innate immunity and inflammatory responses.
0.94 TLR7; and rs3764880 from TLR8) by examination of 795 SLE patients (68 males and 727 females) and 1162 healthy controls (513 males and 649 females).
0.90 TLR8 is phylogenetically related to TLR7 and also mediates recognition of viral ssRNA.
0.82 TLR7 and TLR8 SNPs rs3853839, rs5935436, rs179010 and rs3764880 in the female healthy controls were presented.
0.81 TLR7, and TLR8 were genotyped to determine their associations with systemic lupus erythematosus (SLE) and clinical manifestations of SLE.
0.79 TLR7 rs3853839-G (G vs. C: p = 0.0100) and TLR8 rs3764880-G (recessive model: p = 0.0173; additive model: p = 0.0161) were associated with pericardial effusion in females relative to healthy females.
0.79 TLR7-TLR8 region, although they did not confirm the male specific association.
0.72 TLR7 rs3853839 and TLR8 rs3764880 increased risk of SLE in females (age adjusted p = 0.0032).
0.66 TLR7 and TLR8 contribute to antigen recognition and antibody production in the pathogenesis of SLE.
16286015 0.98 TLR-7), 3M-2 (3 mug/ml, TLR-8), R-848 (5 mug/ml, TLR-7/8), CpG-C274 (5 mug/ml, TLR-9), HSV-1 (MOI: 1), VSV (MOI: 1).
0.97 TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.
0.97 TLR-7 (3M-13, R-848), TLR-8 (3M-2, R-848), and TLR-9 (CpG-C274, selected from various CpG oligonucleotides based on potent IFN-alpha/beta-inducing capacity) induced detectable levels of IFN-alpha ( Figure 1A), IFN-beta (Figure 1B), and IFN-lambda1 (also known as IL-29, referred to hereafter as IFN-lambda; data not shown) in the supernatant, as measured by ELISA after 24 hr of stimulation.
0.97 TLR-7 and TLR-8 agonists, we used the imidazoquinoline compounds R-848, 3M-2, and 3M-13 and GU-rich ssRNAs 33 and 40 and, as a TLR-9 agonist, the potent IFN-alpha/beta inducer CpG-C. We also showed that IRAK-4-deficient monocytes and EBV-B cells did not activate IRAK-1 in response to TLR-7/8 stimulation.
0.97 TLR-7), B cells (TLR-7 and TLR-9), NK cells (TLR-3 and TLR-9), and the main producers of IFN-alpha/beta and IFN-lambda:monocytes (TLR-4 and TLR-8), MDCs (TLR-3), and PDCs (TLR-7 and -9).
0.96 TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells.
0.93 TLR-7, TLR-8, and TLR-9.
0.86 TLR7/8), 3M-13 (3 mug/ml, TLR7), and 3M-2 (3 mug/ml, TLR8) stimulation.
31940779 0.98 TLR7/8, while AU-rich 4-mers seemed to be restricted to human TLR8 activation in immune cells.
0.97 TLR7 and/or TLR8, in a sequence-specific fashion.
0.97 TLR7, as well as human TLR8 in our TLR reporter cell system (see above).
0.94 TLR7/8 signaling activators, we made use of HEK-Blue reporter cells overexpressing human TLR7, human TLR8, murine TLR7, or murine TLR8.
0.90 TLR7 and TLR8 located in endosomes, mediating an inflammatory response against invading viruses and bacteria by sensing GU- and AU-rich single-stranded RNA (ssRNA).
0.89 TLR7 and human TLR8.
0.80 TLR7 and human TLR8 induced the release of various cytokines and chemokines from murine microglia as well as TNF from human-derived monocytes.
0.79 TLR8, our findings may indicate a possible role of these miRNAs as TLR7/8 activators in human CNS diseases.
23314908 0.98 TLR7 and TLR8 receptors, and other than the original landmark studies performed by investigators at 3M Pharmaceuticals, structure-activity relationships in the thiazoloquinoline chemotype remains poorly explored; qualitative assays for TNF-alpha and IFN-alpha induction in human blood were performed in initial studies by 3M as surrogate biomarkers of immunostimulation, and no data on TLR-7 and -8 specific agonistic activities exist in the literature.
0.96 TLR7 and TLR8), double stranded RNA (TLR3), CpG motif-containing DNA (recognized by TLR9), and profilin present on uropathogenic bacteria (TLR11).
0.96 TLR8/TLR7-agonistic properties, elicits adjuvanticity with greater consistency and uniformity, as evidenced by narrower confidence intervals of antibody titers (Fig. 6).
0.96 TLR8 and TLR7 agonistic potencies of the C2-alkyl thiazoloquinoline homologues.
0.94 hTLR8 and hTLR7 reporter gene assays (Fig. 1).
0.92 TLR8- and TLR7-specific NF-kappaB induction profiles of branched-chain and trifluoromethyl analogues of 8c and 8d.
0.82 TLR7 and TLR8-specific reporter gene assays, these analogues exhibited mixed TLR8/TLR7 agonism; the EC50 values of 8c (CL075) were found to be 1.32 muM and 5.48 muM, in TLR8 and TLR7 assays, respectively (Fig. 1, Table 1).
19527497 0.98 TLR7 and TLR8, located in the endosome, act as anti-viral receptors for recognizing single strand RNA (ssRNA), which is present at various phases of viral infection from viral entry to replication.
0.95 TLR 7/8 has been reported to simulate the effects of ssRNA viruses on TLR 7/8, to prime human neutrophils, and then increase the biosynthesis of lipid mediators through NF-kB activation suggesting that TLR7 and TLR8 activation might affect the neutrophilic responses.
0.94 TLR7 and TLR8.
0.92 TLR8, and that the TLR 7/8 ligand R848, but not the TLR7 ligand, induced IL-8 release from neutrophils.
0.73 TLR7 and TLR8 are activated by ssRNA, their signals are transduced through myeloid differentiation primary response gene 88 (MyD-88) and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) leading to enhanced nuclear factor-kappa B (NF-kB) DNA binding activity.
0.57 TLR8, but not TLR7, augmented IL-8 release.
18652679 0.98 TLR7 agonist, 3M-002 will be referred to as a TLR8 agonist, 3M-003 will be referred to as a TLR7/8 agonist, and CpG2009 will be referred to as a TLR9 agonist.
0.97 TLR8 while 3M-002 can activate through TLR7.
0.97 TLR8 agonist 3M-002, which is likely due to residual NF-kappaB activation through TLR7.
0.56 TLR7 and TLR9 agonists induced the production of IgM and IgG. A TLR8-selective agonist was comparatively ineffective at stimulating purified human B cells.
20528831 0.98 TLR7+ epithelial cells of epididymis x 175, (c) TLR8+ epithelial cells of epididymis x 175, (d) TLR9+ epithelial cells of epididymis x 175 and (e) TLR7+ intraepithelial cell in prostate gland x 250.
0.59 TLR7+ intraepithelial cells ranging from few to many were also detected (15 samples from 15 patients) (Fig. 3d,e) A small number of TLR8+ and TLR9+ cells were present in the lamina propria of a few prostate tissues.
24813206 0.97 TLR7 and TLR8 thus appears to be relatively non-specific with ligand recognition being a separate event dependent on the presence of activation determinants (e.g. G/U-richness).
0.97 TLR7 and TLR8 was influenced by two spatially distant sites (distance between site 1a and site 2 of ~60 A) was unexpected as R848 in its longest dimension only spans ~9 A (cf.
0.97 TLR7 and TLR8 and hint to a model of activation shared by other nucleic acid-detecting TLRs and involving multiple signaling 'modes'.
0.97 TLR7 or TLR8 ligands in vivo, our study suggests each class (ORN vs. imidazoquinolines) may lead to a distinct combination of cell type-specific favorable and unwanted cellular effects.
0.97 TLR7, and R53E and H566E in TLR8 show significantly different activation between R848 and RNA40 treatment.
0.97 TLR7 or TLR8 were precipitated with biotin-labeled RNA40.
0.95 TLR7- (A, C) or TLR8-HA (B, D).
0.94 TLR7 or TLR8 defective in RNA40 sensing would also impact R848 recognition.
0.94 TLR7 and TLR8, at least in terms of RNA recognition.
0.94 TLR7 and TLR8 loss-of-function mutants
0.93 TLR7 and TLR8 can signal in two different 'modes' depending on the class of ligand.
0.93 TLR7 and TLR8, it is of fundamental interest and warrants future experimental investigation, not least as aggregation/sequential arrangement would influence the pharmacological properties of imidazoquinolines.
0.92 TLR7 or TLR8 (Fig. 4E, F).
0.92 TLR7 and TLR8 agonists which elicit clinically desirable receptor outcomes.
0.92 TLR7 (A) or TLR8 (B), stimulated with RNA vs. R848 and analyzed for NF-kappaB-activation by dual luciferase assay.
0.90 TLR7 and TLR8 single point mutants (A, B) or mutants harboring multiple mutations (C, D, E) are precipitated in similar ratios compared to WT (A - D) Receptor pull-down using 3'-biotinylated RNA40 reveals intact binding for loss-of-function mutants of TLR7 and TLR8.
0.89 TLR7 and TLR8 sense bacterial and viral RNA, and TLR9 detects bacterial and viral nucleic acids containing CpG motifs, respectively.
0.88 TLR7 and/or TLR8 and, due to their ability to induce type I IFN, are considered antiviral and antitumor therapeutic molecules.
0.88 TLR7 and/or TLR8 ligands, namely RNA ORN and imidazoquinolines, have been considered functionally congruent and interchangeable since so far no significant differences in the outcome of TLR7 or TLR8 activation by RNA ORN vs. R848 have been reported.
0.87 TLR8 but in order to investigate if any differences were exclusive for TLR8 or might extend to the closely related TLR7, the latter receptor was also included in the analysis.
0.86 TLR7 and TLR8 evolutionary genetics study recently proposed low non-synonymous allele frequencies in TLR7 and TLR8 may reflect purifying selection, based on the assumption that viral infection has profoundly influenced human allelic inheritance.
0.85 TLR7 and TLR8 resulted in drastically reduced R848-triggered NF-kappaB activation, which was unexpected for a small ligand.
0.82 TLR7 or 8 agonists, we sought to determine functional outcomes of TLR8 activation by RNA ORN vs. R848 in terms of gene transcription and phospho-proteomics in primary human monocyte-derived DCs (MoDCs).
0.81 TLR7 or TLR8 mutants were then assayed for their ability to activate NF-kappaB in HEK293T cells, a well-characterized model system for such structure-function analyses.
0.75 TLR7 and TLR8
0.75 TLR8, but neither contain TLR7 mRNA (Fig. 1A) nor respond to Imiquimod, a strict TLR7 agonist (Fig. 1B).
0.73 TLR7 and TLR8 residues discriminate between the two structural different ligands
0.73 TLR7 and 2.5 mug/ml for TLR8) and RNA40 (hashed, 12 mug/ml) and the NF-kappaB-activation data measured by dual luciferase assay determined and normalized to the level of WT (as 100%).
0.70 TLR7 and TLR8, contain 'irregular' LRRs with amino acid insertions thought to protrude from the LRR backbone.
0.70 TLR7 R186E and Y579A, and TLR8 R53E responded normally to R848 but not RNA40, whilst the response of TLR8 H566E, and to a lesser extent TLR7 K328E, was greater for RNA40 than R848 (mutations highlighted in green in Fig.4A, B).
0.68 TLR7 and TLR8 ECD
0.59 TLR7-HA (E) or TLR8-HA (F) constructs or an empty vector were analyzed by anti-HA and anti-tubulin immunoblot (loading control).
0.58 TLR7, or TNF via TLR8 in monocytes.
0.57 TLR7 and TLR8 mutants in N- or C-terminal patches is compromised.
0.54 TLR7 and TLR8 are most closely related to TLR9 and TLR3; hence an RNA recognition mechanism similar to TLR9 and TLR3 appears likely.
0.54 TLR7 and TLR8, N-terminal recognition residues are less conserved (not shown) which may explain differences in ligand preference amongst different imidazoquinolines.
0.51 TLR7 or TLR8 that mapped to these sites were functionally tested.
22857391 0.97 TLR7-TLR8 gene region were associated with allergic rhinitis in one Swedish and one Chinese population.
0.97 TLR7, TLR8 and TLR9).
0.97 TLR7 and TLR8 genes, a later study investigated the possible role of these genes in the development of atopic disease.
0.97 TLR7-TLR8 gene region was associated with AR in one Swedish and one Chinese population.
0.96 TLR7 and TLR8) and CpG DNA (TLR9) and some of the TLRs can even recognize several unrelated ligands.
0.96 TLR7 each showed one SNP, and TLR8 had three SNPs with uncorrected P-values below 0.05 (Additional file 4).
0.96 TLR7-TLR8 region in the extended Swedish population
0.96 TLR7-TLR8 gene region was further investigated using a set of 24 SNPs.
0.96 TLR7-TLR8 region in the Chinese population was investigated using Haploview and HapMap CHB data.
0.95 TLR7 and one haploblock spanning the last part of TLR7, the intergenic region and the complete TLR8 gene (Additional file 6).
0.94 TLR7 or TLR8 genes.
0.89 TLR7-TLR8 region.
0.84 TLR7-TLR8 gene region.
0.84 TLR7-TLR8 region in the Chinese population
0.84 TLR7 and TLR8 and the results of the two studies cannot be directly compared for these two genes.
0.82 TLR7TLR8 gene region influences the risk for and the degree of AR: 1) The a priori indicated TLR7 and TLR8 genes gave the strongest signals among the tested TLR genes.
0.82 TLR7-TLR8 gene region.
0.77 TLR8, 2) one additional SNP with a P-value below 0.05 was found in TLR7, and 3) the TLR7 and TLR8 genes are located in the same chromosome region.
0.77 TLR7 and rs2407992 in TLR8.
0.73 TLR7 and TLR8 genes were a priory implicated.
0.68 TLR7 and TLR8 and occurrence and degree of AR, two discordant observations have been made.
0.62 TLR7-TLR8 gene region.
20832340 0.97 TLR8 and TLR7.
0.97 TLR7 and TLR8 agonists (Figure 5A), followed 90 min later by Jun N-terminal kinases (JNK) phosphorylation (Figure 5A).
0.97 TLR7 and TLR8 agonists.
0.97 TLR7 and TLR8 have evolved under strong selection, indicating an essential role in host survival.
0.97 TLR8 agonist (3M2, open bars) or TLR7 agonist (3M13, closed bars) for 0, 30, and 120 min at 37 C. Data are presented as mean fold increase from vehicle control treated cells from three independent experiments.
0.96 TLR7, TLR8, and TLR9), monocytes weakly express TLR3 and TLR9 and do not respond to TLR3 and TLR9 agonists (Figure S3).
0.95 TLR7 and TLR8 agonists.
0.95 TLR7, TLR8, and TLR9 (UNC-93B deficiency) share the narrow viral phenotype of TLR3-deficient patients, with herpes simplex encephalitis.
0.94 TLR8 agonists (3M2 and R848) and to a lesser extent to a TLR7 agonist (3M13) was similar to their response to intact viruses.
0.93 TLR7-TLR 8-MYD88-MEK-Dependent Pathway
0.91 TLR7-TLR8 agonists, and viruses, ribonucleoprotein-containing immune complexes induce CCL3 and TNF-alpha production by CD14dim monocytes.
0.90 TLR7- TLR8 agonists between that of CD14dim and CD14+CD16- monocytes, and future studies will need to investigate potential heterogeneity of this "double positive" population.
0.89 TLR7 and TLR8 for cytokine production, we purified CD14dim and CD14+ CD16- monocytes from the peripheral blood of patients deficient in myeloid differentiation primary response gene 88 (MYD88) and in some cases in interleukin-1 receptor-associated kinase 4 (IRAK-4) and from controls and were stimulated with measles virus and/or HSV1.
0.89 TLR7 and TLR8 to detect viruses and nucleic acids for the production of the proinflammatory cytokines TNF-alpha and IL-1beta further suggests that TLR7 and TLR8 are endowed with an essential physiological role.
0.85 TLR7-TLR8 expressing monocytes, our results indicate that activation of CD14dim monocytes by endogenous nucleic acids can contribute to the pathogenesis of inflammatory autoimmune diseases such as SLE, during which immune complexes containing nucleoproteins accumulate in tissues and in particular the glomeruli.
0.84 TLR7, TLR8, and TLR9.
0.81 TLR7 and TLR8 are apparently redundant for host defense against most common viruses, although it is possible that TLR7 and TLR8 are required for the defense against yet unidentified virus(es).
0.80 TLR7 and TLR8 signaling in monocyte subsets simulates in silico TNF-alpha, IL-1beta, IL-8, and IL-6 expression profiles that are consistent with our experimental data.
23151919 0.97 TLR7 agonists used in clinical trials has shown to trigger TLR8 response.
0.97 TLR7, TLR8, and TLR9 to inhibit progression of SLE and other autoimmune diseases at an early stage by blocking inappropriate TLR activation.
0.96 TLR7 preferentially recognizes GU-rich RNA sequences and TLR8 has more affinity for AU-rich sequences.
0.96 TLR8 stimulation inhibits TLR7 response.
0.96 TLR7 and TLR8.
0.96 TLR7-transfected cells and at 4 microM in TLR8-transfected cells.
0.94 TLR7 and TLR8 respond to synthetic ssRNA and certain synthetic nucleoside analogues, such as guanosine-containing compounds and imidazoquinoline.
0.92 TLR7 and TLR8 share sequence similarity and recognize the same native pathogen.
0.91 TLR7, TLR8, and TLR9 differentiate between host- and pathogen-derived nucleic acid.
0.90 TLR7, TLR8 and TLR9 pathways.
0.89 TLR7, TLR8, and TLR9
0.87 TLR7, TLR8, and TLR9 localize within various intracellular compartments.
0.78 TLR7, TLR8, and TLR9 depend on the MyD88-dependent pathway with the exception of TLR3, which exclusively uses the TRIF-dependent pathway to induce expression of proinflammatory cytokines.
0.78 TLR7 and TLR8 usually necessitates cellular uptake of these receptors.
0.76 TLR7 and TLR8.
0.70 TLR7, TLR8, and/or TLR9 pathways by chromatin- or RNA-containing immune complexes leading to autoantibody production.
0.68 TLR7 and TLR8 has not been defined as it has for TLR9 (hexameric CpG); however, ssRNA sequences containing GU-rich or poly-U sequences can trigger both receptors.
0.65 TLR7, TLR8, and TLR9 induces IRF7, leading to the production of typeI IFNs.
30699960 0.97 TLR7, and TLR8 in humans and TLR13 in mice.
0.97 TLR8 and TLR7 in trans, respectively.
0.96 TLR7 and TLR8 as identified by Schmidt et al., it is probable that this "specificity" is not a general effect but very much dependent on the specific sequence context of the modification.
0.95 TLR7 (DmDN) but not TLR8 (DmRC).
0.95 TLR7 and TLR8.
0.93 TLR7 binds a polyU 3-mer and is located in the dimerization interface, whereas the second binding site of TLR8 is localized outside the dimerization interface and senses UG or UUG oligoribonucleotides.
0.93 TLR7 and TLR8.
0.89 TLR7 and TLR8 dimers bound to their specific ligands have been identified.
0.88 TLR7 and TLR8 in humans, in mice TLR7 and TLR13 are the relevant receptors.
0.87 TLR7, TLR8, TLR9, and TLR13 which reside in the endosome.
0.86 TLR7 and TLR8 within pDCs and monocytes, respectively.
0.83 TLR7, and TLR8.
0.81 TLR7 activity while retaining TLR8 stimulation.
0.67 TLR7 and TLR8 activation.
0.63 TLR7 and TLR8, which is responsible for RNA sensing, differs regarding sequence specificity and localization.
0.54 TLR7 or TLR8 response.
27498757 0.97 TLR7 rs179008, TLR8 rs4207992, TLR9 rs187084 and TLR10 rs4219009 polymorphisms.
0.97 TLR7, TLR8, TLR9 and TLR10 genes as risk factors for bronchiolitis, early-childhood wheezing and childhood asthma are mainly lacking, our study was an exploratory one with no purpose to test hypotheses, but rather to produce hypotheses for later confirmatory studies.
0.96 TLR7, TLR8 and TLR9 recognize viral products responding to viral double-stranded (ds) RNA, viral single-stranded (ss) RNA or cytotoxic granule proteins containing DNA from certain bacteria and some viruses, respectively.
0.96 TLR7 and TLR8 polymorphisms were associated with asthma and allergic rhinitis.
0.94 TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 or TLR10 rs4129009 polymorphisms and viral findings, clinical characteristics or subsequent wheezing in infants with bronchiolitis.
0.92 TLR7 rs179008 and TLR8 rs2407992 are located on the X chromosome, the data are given separately for boys and girls.
0.92 TLR7 and TLR8 genes are located on the X chromosome, HWE was not studied.
0.91 TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 and TLR10 rs4129009 polymorphisms are associated with the presence, clinical characteristics and viral etiology of bronchiolitis in early infancy.
0.88 TLR7 and TLR8 genes are related to asthma and allergy, as well as to susceptibility to respiratory viral infections.
0.88 TLR7 rs179008, TLR8 rs4207992, TLR9 rs187084 and TLR10 rs4219009 were not associated with the characteristics of bronchiolitis, including those reflecting bronchiolitis severity.
0.88 TLR7 rs179008 and TLR8 rs4207992 gene polymorphisms, located on the X chromosome, were not associated with post-bronchiolitis outcome measures in either boys or girls.
0.87 TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 or TLR10 rs4219009 polymorphisms (Table 1).
0.68 TLR7 rs179008, TLR8 rs4207992, TLR9 rs187084 or TLR10 rs4219009 gene polymorphisms and characteristics of bronchiolitis in early infancy or post-bronchiolitis outcomes.
0.52 TLR7 rs179008, TLR8 rs4207992, TLR9 rs187084 or TLR10 rs4219009 polymorphisms.
19234187 0.97 TLR7 and/or TLR8 are engaged, NF-kappaB and other transcription factors are activated, leading to the transcription of immune response related genes, including cytokine, chemokine, co-stimulatory marker, and adhesion molecule genes.
0.97 TLR7 activation primarily leads to the production of IFN-alpha and IFN-regulated cytokines, which is similar to TLR9 activation, while TLR8 is functionally associated with the production of pro-inflammatory cytokines, such as TNF- alpha.
0.97 TLR8-mediated activation of NF-kappaB and JNK are dependent on MEK kinase 3 (MEKK3), while TLR7-mediated activation of NF-kappaB is transforming growth factor-beta-activated kinase 1 (TAK-1) dependent.
0.96 TLR7 and TLR8 agonists induced a slightly greater up-regulation of surface markers on LC that have previously been exposed to HPV16 VLP than on untreated LC, however these differences in expression are not statistically significant.
0.96 TLR8 agonists, such as 3M-002 and resiquimod, are more effective in inducing LC activation and overcoming the tolerizing-like phenotype and function of LC exposed to HPV16 VLP, in comparison to TLR7 agonists, such as imiquimod.
0.96 TLR8 and TLR7 results in inhibition of TLR7 to respond to its agonist.
0.96 TLR8 may inhibit LC from responding to agonists that preferentially bind TLR7, which explains why TLR8 dominant agonists (such as 3M-002 and resiquimod) are more effective than TLR7 dominant agonists (such as imiquimod and potentially 3M-031) in activating LC and in driving a strong cell-mediated immune response.
0.95 TLR8 agonists are more effective than TLR7 agonists at inducing pro-inflammatory cytokines and chemokines by monocyte-derived DC (GM-CSF/IL-4/TGF-beta).
0.94 Toll-like receptor 7 (TLR7) and TLR8 are expressed on human LC, we hypothesized that imidazoquinolines would activate LC exposed to HPV16, leading to the induction of an HPV16-specific cell-mediated immune response.
0.93 TLR7 and TLR8 is the difference in the signal transduction pathways initiated by each of the receptors.
0.90 TLR7 and/or TLR8 agonists as a means to initiate the activation of HPV16 infected LC, thereby inducing an effective cell-mediated immune response against HPV16.
0.88 TLR7 and TLR8 agonists, however, resiquimod is much more effective in activating LC.
0.85 TLR7 and/or TLR8 agonists and therefore are potent innate immune modulators (Table 1,).
23468661 0.97 TLR7-TLR8 region on Xp22.2.
0.97 TLR7-TLR8 region with SLE.
0.96 TLR7-TLR8 region and the location of all studied SNPs are indicated.
0.96 TLR7 or TLR8 mRNA levels were observed between individuals carrying the same genotype [GG women vs. G men: P = 0.41 (TLR7), 0.63 (TLR8a) and 0.50 (TLR8b); CC women vs. C men: P = 0.10 (TLR7), 0.91 (TLR8a) and 0.65 (TLR8b)].
0.96 TLR7 rather than TLR8 gene expression.
0.96 TLR7 and TLR8 proteins by flow cytometry in PBMCs from 7 pairs of healthy women (GG vs. CC) and men (G vs. C), respectively.
0.95 TLR7-TLR8 region, we confirmed that the previously reported functional SNP rs3853839, located within a predicted binding site of miR-3148, was most likely responsible for observed association with SLE in three populations of non-Asian ancestry.
0.94 TLR7 3'downstream to TLR8 intron 1 were consistently associated with SLE (P<0.05) in EA, AA and HS (Table S1), and remained significant trans-ancestral meta-analysis P values after Bonferroni correction (5.5x10-6<=Pmeta<=1.3x10-6, Table S1).
0.93 TLR7-TLR8 region exhibiting consistent and independent association with SLE (P meta = 7.5x10-11, OR = 1.24 [1.18-1.34]).
0.93 TLR7-TLR8 region and confirmed rs3853839 exhibiting the strongest association with SLE in European Americans, African Americans, and Amerindian/Hispanics.
0.90 TLR7 and TLR8 that was not well imputed in this study.
0.83 TLR7 copies in childhood-onset SLE patients, no evidence for common CNVs at the TLR7-TLR8 region has been identified in individuals of diverse ancestries through our previous study by three independent methods including quantitative real-time PCR, PmeI pulsed-field gel electrophoresis and Southern blot, two recent studies using customized CGH platforms as well as other studies listed in the Database of Genomic Variants (http://projects.tcag.ca/variation; the latest version released in November 2010), suggesting that mutations similar to Yaa are not a frequent feature of human SLE.
0.69 TLR7 3'UTR) as the most likely polymorphism responsible for the association of TLR7-TLR8 region with SLE in individuals of EA, AA and HS ancestry, and have characterized a differential miR-3148 modulation which explains the effect of allelic variation of rs3853839 on TLR7 expression.
25192394 0.97 TLR7 is expressed in plasmacytoid dendritic cells (pDC) and B cells, whereas TLR8 is mainly expressed in conventional/myeloid dendritic cells (cDCs), monocytes, macrophages, and neutrophils.
0.97 TLR7 and TLR8 agonists.
0.96 TLR7/8 activity, pointed strongly also to the strict dependence of the selectivity for TLR7 vis-a-vis TLR8 on the electronic configurations of the heterocyclic systems, the nuances of which we desired to examine quantitatively with the goal of developing "heuristics" to clearly define structural requisites governing activity at TLR7 and/or TLR8.
0.94 TLR7/8 activators pointed to the strict dependence of the selectivity for TLR7 vis-a-vis TLR8 on the electronic configurations of the heterocyclic systems, which we sought to examine quantitatively with the goal of developing "heuristics" to define structural requisites governing activity at TLR7 and/or TLR8.
0.94 TLR8 agonism in the 2-butylfuro[2,3-c]quinolin-4-amine 5, but further strengthened the case for a systematic exploration of the role of electron densities in the heterocyclic core in determining TLR7/8 activity.
0.93 TLR7- and TLR8-agonistic potencies (EC50 values) of the compounds determined in TLR-specific reporter gene assays.
0.93 TLR7 agonistic activity (9, 11, and 53) showed IFN-alpha inducing ability and the TLR8 selective compound 39 did not (Figure 3).
0.93 TLR7 and TLR8 by these analogues.
0.92 TLR7 and TLR8.
0.92 TLR8-specific), and group 2 (TLR7/8 dual-active) compounds obtained via linear discriminant analyses of Mulliken charges.
0.90 TLR7 and TLR8 are single-stranded RNA (ssRNA); these endosomal TLRs can also be activated by synthetic small molecule TLR7/8 agonists.
0.74 TLR8-active (coded "1"), and TLR7/8 dual-active (coded "2") compounds (Figure 8B).
0.55 TLR7 and TLR8 agonism assays, and the oxazolo[5,4-c]quinoline derivative (22b) was found to possess negligibly low TLR8-agonistic activity.
28013457 0.97 TLR7, TLR8, and TLR9 were sequenced in ten bats.
0.97 TLR7, TLR8, and TLR9 is still in progress.
0.95 TLR7, TLR8, and TLR9 were under purifying selection, consistent with previous studies (Areal et al.; Cowled et al.; Escalera-Zamudio et al.; Schad and Voigt; Zhang et al.).
0.94 TLR7, TLR8, and TLR9.
0.90 TLR7, TLR8, and TLR9.
0.90 TLR7, TLR8, and TLR9 might contribute to the adaptation of pathogen-host interaction in bats, especially in bat TLR9.
0.89 TLR7, TLR8, and TLR9 evolved under positive selection.
0.84 TLR7, TLR8, and TLR9 was that the bat ancestor was positively selected in the long-term evolution, which was also detected by Escalera-Zamudio et al.. However, in a similar study for TLR8, the ancestor of bats was not detected (Schad and Voigt).
0.81 TLR7, TLR8, and TLR9 are involved in virus recognition.
0.62 TLR8 and TLR7.
0.61 TLR7, TLR8, and TLR9 that are responsible for detecting RNA and DNA pathogens.
0.61 TLR7, c TLR8, and d TLR9.
22164301 0.97 TLR8 is phylogenetically and structurally related to TLR7; they both recognize ssRNA and an imidazoquinoline compound.
0.96 TLR7 and TLR9 are selectively expressed in B cells and plasmacytoid DCs, while TLR3 and TLR8 are expressed in myeloid DCs.
0.96 TLR8 differed from TLR7 and TLR9, both of which reside in the endolysosome and the ER.
0.94 TLR8 is phylogenetically and structurally related to TLR7 and TLR9, but little is known about its localization or function.
0.94 TLR8, like TLR3, is localized to the early endosome but not in the late endosome/lysosome, where TLR7 and TLR9 reside.
0.92 TLR7 and TLR9 to endolysosomes where the receptors are cleaved by proteases, this is not the case for TLR8 or TLR3.
0.91 TLR7 and TLR8 recognize sequence-specific ssRNA and imidazoquinoline compounds in distinct cells and organelles, resulting in the induction of different immune responses via the same adaptor protein, MyD88.
0.87 TLR8 are expressed in myeloid DCs, while TLR7 and TLR9 are expressed in plasmacytoid DCs.
0.84 TLR7 ligands induce IFN-alpha production by plasmacytoid DCs, while TLR8 ligands induce proinflammatory cytokine production (e.g., TNF-alpha and IL-6) by myeloid DCs and monocytes.
0.73 TLR8 seems to differ from TLR7 and TLR9 in its mode of ligand recognition.
0.71 TLR8 belongs to the TLR7/8/9 subfamily, the present study demonstrated that TLR8 possesses properties distinct from those of TLR7 and TLR9.
27402566 0.97 TLR7/8 agonists and interact with human TLR7 and TLR8, but do so with highly variable potency (Figure 1).
0.97 TLR7- or TLR8-induced NF-kappaB activity versus control with half maximal effective concentrations (EC50) for each compound determined by non-linear curve fitting, numbers in parenthesis represent the 95% upper and lower confidence intervals.
0.96 TLR7 is predominantly expressed in pDCs and TLR8 is expressed exclusively in mDCs, therefore it would be expected that agonists with highest activity in the HEK TLR7 assays would be more potent towards pDCs and more TLR8 selective agonists would be more potent in mDCs.
0.95 hTLR7 vs. hTLR8 receptor - i.e. the ratio of TLR7 EC50 to TLR8 EC50.
0.94 hTLR8, it was essentially unable to bind hTLR7 (Figure 1).
0.92 TLR7 and TLR8 responsiveness closer to humans than rodents (Figure 5 and), was chosen as a model system.
0.91 hTLR7 or hTLR8 cells were subjected to treatment with increasing concentrations of compound 7 followed by determination of relative NF-kappaB activity versus control using a QuantiBlue colorimetric assay.
0.88 TLR7/TLR8 potency than compound 4 (and any compounds tested prior; data not shown), with 3-/8-fold greater TLR7/TLR8 potency (Figure 5A vs. Figure 1).
0.87 hTLR7 or hTLR8 cell response to compound 7, right.
0.80 hTLR7 or hTLR8 were treated with increasing concentrations of the compounds and the potency of each compound was determined (Figure 1B).
0.55 TLR7, but not TLR8.
28582454 0.97 TLR7 and TLR8, which function in immune responses against viral infections.
0.97 TLR7 and TLR8 binding pocket, which yield functional differences for both receptors, as previously proposed by Gorden et al.. Additionally, because of their different hydrophobic side chains, IMMS may possess TLR selectivity similar to that reported for R837 (imiquimod), which specifically activates TLR7.
0.97 TLR7 and TLR8 similarly to the natural pathogens to yield a cascade of biochemical events that initially stimulate several type of cells, such as monocytes and NK/NKT, T, B, mast and tumor cells.
0.95 TLR7 and TLR8 sense single-stranded viral RNA.
0.94 TLR7 and TLR8.
0.94 TLR7 and TLR8.
0.93 TLR7 and TLR8 to the same TLR subfamily, showing a high level of sequence homology.
0.91 TLR7 with respect to TLR8.
0.90 TLR7 and TLR8.
0.83 TLR8, whereas Hybrid-2, CL097 and R848 are more effective for TLR7.
0.51 TLR7 and TLR8 in the same IMMS.
22239408 0.97 TLR7 and TLR8 modulatory activities of dimeric constructs of imidazoquinoline linked at the C2, C4, C8, and N1-aryl positions.
0.94 TLR7 and TLR8 whose endogenous ligands are single-stranded viral RNA (ssRNA), recognize and transduce signals upon engagement by small, non-polymeric molecules such as the imidazoquinolines; and the oxoadenines.; We were not only desirous of examining the effect of variously configured, pre-organized dimeric constructs of the imidazoquinolines on TLR7 and TLR8 in our continuing efforts to identify efficacious and safe vaccine adjuvants, but also motivated in the hope that we may, by design or accident, discover small-molecule modulators of TLR3.
0.94 TLR7, but not TLR8 signaling via inhibition of endolysosomal acidification.; We found 4a to be a potent inhibitor of both TLR7 and TLR8-induced cytokine and chemokine release with IC50 values of about 0.05-0.3 muM (Figs 4, 5).
0.93 TLR7-specific agonist) or CL075 (TLR8-specific agonist) was used at a starting concentration of 20 mug/mL, and were two-fold diluted serially (along the rows).
0.89 TLR7- and TLR8-mediated chemokine production in human peripheral blood mononuclear cells by chloroquine or 4a.
0.85 TLR7 inhibition by 4a is near-ideal (slope: 1.12, Fig. 6), a distinct deviation from ideal competitive inhibition for TLR8 is observed (slope: 0.51), suggesting that additional mechanisms for TLR8 inhibition, possibly allosteric, may be operational.
0.85 TLR7- and TLR8-induced activation.
0.79 TLR7- and TLR8-mediated proinflammatory cytokine production in human peripheral blood mononuclear cells by chloroquine or 4a.
0.77 TLR8 agonist) or gardiquimod (TLR7 agonist).
0.66 TLR8 signaling manifests predominantly in the induction of pro-inflammatory cytokines such as TNF-alpha and IL-1beta.; Chloroquine, a TLR7 antagonist, is a feeble inhibitor of TNF-alpha and IL-1beta, while 4a, as would be expected for a TLR8 antagonist, potently inhibits the production of these proinflammatory cytokines (Fig. 4), as well as IL-6 and IL-8 which are typically induced secondarily, in an autocrine/paracrine manner.
28919783 0.97 TLR7 and TLR8 have been used as targeted therapies in a variety of cancers, including pancreatic and bladder cancers, basal cell carcinoma, and melanoma.
0.97 TLR7 and TLR8 (r=0.8903, P<0.0001, Table 1).
0.96 TLR7 and TLR8 were also highly correlated with the expressions of CD8 and other functional markers of CD8+ T cells.
0.96 TLR7 and TLR8 (TLR7/8) are expressed in immune cells, including dendritic cells (DCs), as well as in keratinocytes and melanoma cells.
0.96 TLR8 is phylogenetically related to TLR7 and, like TLR7, binds to viral ssRNAs and foreign bacteria.
0.96 TLR7 and TLR8 expression levels.
0.94 TLR7 and TLR8 in melanoma tumors is associated with high expression levels of functional markers of immune cells, which predicts longer overall survival of patients with melanoma.
0.84 TLR7 and TLR8 genes are located in human chromosome Xp22.2.
0.81 TLR7 (C) and TLR8 (D).
0.63 TLR7 or TLR8 expression predicted better clinical outcome for melanoma patients (TLR7: HR =1.734, P<0.0001; TLR8: HR =2.072, P<0.0001).
30453684 0.97 TLR7 and/or TLR8 (Figure 3A).
0.97 TLR7 and/or TLR8 had different consequences for viral replication in each cell line.
0.97 TLR7, TLR8, TLR7 + TLR8, or STAT2 on AXL expression in time-matched mock-infected (UI) and ZIKV-infected (I) HMC3 and JEG-3 cells at one dpi and three dpi. (* p < 0.05).
0.96 TLR7 and TLR8 in the host-pathogen interaction network.
0.96 TLR7 and/or TLR8 showed a strong upregulation of a subset of genes (Figure 5B, left plots) that mostly disappeared when these cells were transfected and infected with ZIKV (Figure 5B, right plots).
0.92 TLR7, TLR8, TLR7 + TLR8, or scramble (control) on the expression of selected innate immune response factors.
0.91 TLR7, TLR8, or TLR7 + TLR8 on ZIKV virus replication in different cell types over time.
0.88 TLR7, TLR8, TLR7/8, and STAT2.
0.66 TLR7, TLR8, and STAT2 during ZIKV infection, since they are key molecules in the cellular antiviral and IFN-mediated responses.
0.54 TLR7, TLR8, or both (Figure 5, Supplementary Figure S2).
23085951 0.97 TLR7, TLR8 and TLR9 are located within intracellular vesicles.
0.95 TLR7 and TLR8 can also detect oligoribonucleotides and a variety of synthetic chemical agonists such as imidazoquinolines.
0.94 TLR7 and TLR9 are upregulated in patients with Sjogren's syndrome, while TLR8 is not.
0.92 TLR8: human TLR8 downregulates TLR7 and TLR9 signalling.
0.90 TLR7 and TLR8 are located in the X chromosome.
0.87 TLR7 in sensing bacterial RNA is now well accepted, a similar role for TLR8 has only began to be uncovered.
0.75 TLR7 and TLR8 are phylogenetically similar and both are capable of recognizing single-stranded RNA and short double-stranded RNA, hence their role in sensing different viral pathogens.
0.59 TLR7, TLR8 and TLR9 are important in sensing foreign nucleic acids encountered by phagocytes.
0.55 TLR8 is known to be primarily expressed in monocytes/macrophages and myeloid dendritic cells (DCs), while TLR7 is predominately expressed in plasmacytoid DCs and, to some extent, in B cells and monocytes/macrophages.
29181003 0.97 TLR7 and TLR8, as both receptors bind to the degradation products of RNA.
0.96 TLR8-/- cells did, however, show a greater decrease in TNF-alpha secretion compared with that of the TLR7-/- cells (Figure 2C).
0.96 TLR8 and, to a lesser extent, through TLR7.
0.95 TLR7 and TLR8 in human immune cells.
0.94 TLR7-/-, TLR8-/-, and TLR7-/- x TLR8-/- BLaER1 monocytes using DOTAP and measured the secretion of TNF-alpha and IL-1beta after 18 h. Similar to whole archaea, RNA from M. stadtmanae is recognized by TLR7 and TLR8, but the knockout of TLR8 revealed that the latter receptor has a stronger effect (Figure 2D).
0.93 TLR7/8 agonist R848, the TLR7 agonist CL264, and the TLR8 agonist TL8-506 were used as controls to confirm the specificity of the clones used in this study (Figure 2C).
0.93 TLR8-/- and TLR7-/- x TLR8-/- cells (Figure 3G) indicating that activation of TLR8 by M. stadtmanae hence leads to induction of pyroptosis.
0.92 TLR8 and to a lesser extent by TLR7.
0.69 TLR7-/-, TLR8-/- or TLR7-/- x TLR8-/- monocytes after stimulation with M. stadtmanae (100:1), 50 ng/mL LPS, or 5 microg/mL R848 for 8 h was measured by qRT-PCR.
29854853 0.97 TLR7 and TLR8 ligands to inhibit HIV replication and to activate the HIV reservoir is being investigated.
0.97 TLR7 and TLR8 ligands were proposed to be used as adjuvants in FLU vaccine preparations.
0.96 TLR7 and TLR8 ligands are potential candidates for antiviral therapeutic and vaccine strategies.
0.95 TLR7 and TLR8 genes were associated with immune responses to MV suggesting a role for both TLRs during MV infection.
0.84 TLR7 or TLR8 in detecting RNA viruses is different depending on the virus and the cell in which these TLRs are expressed.
0.77 TLR7/8 stimulation, and the clearance and progression of the HCV infection is modulated by variations in the TLR7 and TLR8 genes.
0.69 TLR7 and TLR8 genes were associated with the CD4 T cell count during an HIV infection as well as the levels of type 1 IFN and proinflammatory cytokines and the progression to hepatocellular carcinoma during an HCV infection.
0.66 TLR7, and TLR8 are expressed in the endosomes.
0.56 TLRs 7 and 8 were also described for Zika virus (ZIKV) infection, as no TLR7 activation was detected in primary human fibroblasts, while genes implicated in TLR7 and TLR8 pathways were found to be upregulated in the human neural progenitor cells (hNPCs) infected with this virus.
30450666 0.97 TLR7 and TLR8 detect ssRNA, which may explain why one ligand is equally effective against both TLRs.
0.97 TLR7 and TLR8 have the benefit of being targeted by small molecules rather than ssRNA.
0.96 TLR7 and TLR8 share similar activation patterns, both have z-loops involved in ssRNA recognition, and both possess two binding sites; the first binding site binds guanosine and uridine in TLR7 and TLR8, respectively, while the second binds ssRNA in both cases (Figure 3).132 In TLR7 ssRNA binding primes the receptor for guanosine binding and subsequent dimerization, while synthetic molecules, such as R848, can activate TLR7 without the need for ssRNA.133, 134 Importantly, TLR7 remains monomeric in the absence of any ligand and dimerizes in response to ligand binding; however, its dimer conformation is similar to TLR8 and TLR9.
0.93 TLR7 and TLR8 are functionally active in the endosomal compartment, use MyD88 adapter molecules and are activated by single-stranded RNA (ssRNA).123, 124 Majority of ligands in clinical trials that target TLR7/8 are small molecules (eg, imiquimod [R837], resiquimod, or GSK2245035), and most are derivatives of imidazoquinoline, a tricyclic organic molecule.125, 126, 127 (Tables 6, 7, 8).
0.93 TLR8 can also be activated by ssRNA as natural ligand and by VTX-2337 (motolimod), a synthetic small molecule selective for TLR8 and is being evaluated in clinical trials.124, 130 TLR8 is a less studied receptor, as its roles overlap with those of TLR7, with which it shares multiple features.
0.91 TLR7 agonists; however, other than monocytes, TLR8 agonists can directly activate mDCs and monocyte-derived DCs.
0.87 TLR7 agonists were more potent when compared with TLR8 agonists regarding antiviral responses in the form of IFN, I-TAC (IFN-inducible T-cell alpha chemoattractant), and IFN-regulated cytokines from human peripheral blood mononuclear cells (PBMC).128 Proinflammatory responses, such as expression of IL-12, TNF-alpha, and macrophage inflammatory proteins-1alpha (MIP-1alpha) were enhanced by TLR8 agonism when compared with TLR7, leading to characteristic differential cell induction profiles.
0.85 TLR7, TLR8, TLR9, and adjuvant) from June 2017 to Jan 2018.
0.62 TLR7, TLR8, and TLR9 are functionally localized to endosomes (Table 1).1, 5, 6 These receptors invariably work as homodimers or heterodimers, and several studies have suggested that they exhibit unusual dimer characteristics.7, 8 All TLRs form homo- and heterodimers, except for TLR3 and TLR5, which are currently considered strictly homodimeric, in the absence of empirical evidence to the contrary.
22848646 0.97 TLR7 and TLR8 but not TLR3.
0.96 TLR7 and 6/13 placentas for TLR8 exhibited increased levels of these receptors.
0.93 TLR7 and TLR8 staining were not examined.
0.90 TLR7, and TLR8 were increased significantly in women with PE compared to normotensive women.
0.82 TLR7, and TLR8 together is highly associated with PE, but whether these occur prior to the development of PE in women remains to be determined.
0.64 TLR7, and TLR8 compared to normotensive women.
0.62 TLR7, and 2 for TLR8.
0.58 TLR7, and TLR8 play a significant role in the development of PE and may be potential therapeutic targets to diminish the severity of PE symptoms in women.
20542588 0.97 TLR7 alone, they were stimulating either TLR8 (R-0002) or both receptors (R-0006) simultaneously.
0.93 TLR7 ligands whereas the effects were minimal for TLR8 and TLR9 ligands indicating that the suppressive phenotype is unique only for certain TLRs.
0.81 TLR8 and TLR7/8 agonists on T cell activation, we isolated human CD4+ T cells and stimulated them with anti-CD3 antibody.
0.74 TLR7 is expressed on purified CD4+ T cells and TLR8 not.
0.72 TLR7/8 ligand R-848, TLR2/6 ligand Pam3CSK4 and with the phosphorothioate ORN R-0006, containing a sequence motif that activates both TLR7 and TLR8.
0.64 TLR7 would be directly co-stimulated, whereas monocytes expressing TLR8 would deliver a negative signal to the activated T cells, resulting in a block of T cell proliferation.
0.51 TLR7/8 ligand R-848 and the TLR8-specific ORN R-0002 as well showed a similar inhibition, suggesting that the inhibition may be mediated by TLR7 and/or TLR8.
22521247 0.97 TLR7- and TLR8-mediated Mo IL-1beta were largely refractory to adenosine, to our knowledge the first time the effects of adenosine on the inflammasome pathway have been evaluated.
0.95 TLR7 agonist-induced TNF production (p < 0.05), TLR8 agonist-induced TNF was largely refractory (Fig 3, D).
0.95 TLR8 agonists were refractory to the inhibitory effects of adenosine (Fig 3) and accumulated less cAMP than those exposed to a TLR7 agonist (Fig 3, C).
0.94 TLR8-dependent, we further characterized the mechanism of TLR8-induced APC activation and cytokine production in neonatal Mos by assessing the relative sensitivity of TLR7 and TLR8 agonists to the inhibitory adenosine-cAMP axis.
0.86 TLR7 and TLR8 agonists.
0.86 TLR8 agonist 3M-002 induces greater TLR pathway mRNA up-regulation and Th1-polarizing cytokines/chemokines from neonatal Mos than a TLR7 agonist
0.53 TLR7), R848 (TLR7/8) or 3M-002 (TLR8).
23899291 0.97 TLR8 agonism with no detectable signatures of TLR7 activity, allowing for the first time a clear path toward the evaluation of such compounds as potential adjuvants for vaccines.
0.93 TLR7, TLR8, NOD1, as well as C-C chemokine receptor type 1.
0.93 TLR7-active imidazoquinolines, and the TLR8/7-agonistic thiazoloquinolines, but unlike the thiazoloquinolines, 8d was devoid of TLR7-stimulatory activities in primary screens (Fig. 2).
0.86 hTLR8 complexed with mixed TLR7/TLR8-agonistic imidazoquinolines and thiazoloquinolines were reported, allowing us to rationalize our experimentally-determined SAR on the pure TLR8-agonistic furo[2,3-c]quinolines.
0.80 TLR7 and TLR8), double stranded RNA (TLR3), CpG motif-containing DNA (recognized by TLR9), and profilin present on uropathogenic bacteria (TLR11).
0.63 TLR8-dependent, while IFN-alpha production is TLR7-mediated.
0.53 TLR8 activators as potential adjuvants for neonatal vaccines is the availability of pure TLR8 agonists with negligible TLR7 activity and, other than the 2,3-diamino-furo[2,3-c]pyridine class of compounds recently described by us, all other known agonists of TLR8 such as the imidazoquinolines (for instance, 1), thiazoloquinolines (CL075, 2), and a 2-aminobenzazepine derivative (VTX-2337, 3), all display mixed TLR7/TLR8-agonism, with the sole exception of VTX-294, whose complete structure has not been reported.
26784926 0.97 TLR7 and TLR8 recognize components of single stranded-RNA (ss-RNA) including exogenous viral ssRNA and endogenous RNAs, they show distinct expression patterns.
0.97 TLR7 expression is limited to plasmacytoid dendritic cells (pDC) and B-cells, while TLR8 is predominantly expressed by monocytes, macrophages and myeloid dendritic cells (mDCs).
0.93 TLR7 can exist in a pre-formed ligand-independent, oligomeric state similar to TLR8 and TLR9.
0.92 TLR7 and TLR8, but not TLR9, were mutated to the corresponding amino acid in TLR9 (Y356S, V381F, and L557Y/T586G) (S4A Fig).
0.86 TLR7, TLR8 and TLR9 constitute a subfamily of intracellular endo-lysosomal TLRs that recognize components of nucleic acids.
0.83 TLR7 likely stabilizes itself through adopting a homo-dimer conformation independent of ligand, similar to TLR8 and TLR9.
0.75 TLR7 and TLR8, but several residues were identified which differ and may be responsible for the TLR7 selectivity of GS-9620.
28767704 0.97 TLR7 and TLR8.
0.96 TLR7 or TLR8, or both.
0.96 hTLR7 and postulate hTLR8 as a possible receptor.
0.96 TLR7 or TLR8 in their transit through endosomes and lysosomes, although they do not persist in macrophages.
0.91 hTLR7 agonist, Gardiquimod (C) or with different doses of a hTLR7 and hTLR8 agonist, R848 (Resiquimod) (D) in the presence of IFN-gamma for 48 h. THP-1 cells (E and F) were treated with different doses of two hTLR8 agonists, ORN06 (E) and ssRNA40 (F) in the presence of IFN-gamma for 48 h. (G) Murine BMM were treated with different doses of ssRNA40 in the presence of mIFN-gamma for 48 h. (H and I) Murine BMM from TLR7 KO mice were infected with B. abortus (H) or stimulated with different doses of B. abortus RNA (I) in the presence of mIFN-gamma for 48 h. (J) THP-1 cells were treated with ORN06 (10 mug/ml) in the presence of IFN-gamma and Cetuximab or Isotype control for 48 h. MHC-I expression was assessed by flow cytometry.
0.88 TLR8/TLR7 in the cytotoxic CD8+ T cell responses and chronicity of B. abortus-infected mice.
0.87 TLR7 (hTLR7) agonist Gardiquimod, the human TLR7/8 (hTLR7/8) agonist Resiquimod (R848) and the human TLR8 (hTLR8) agonists ssRNA40/LyoVec and ORN06/LyoVec.
29312324 0.97 TLR8 was expressed at higher levels with respect to TLR7 in these cells (Figure S1 in Supplementary Material).
0.95 TLR7/8/9 targeting ODN, whereas the TLR7-specific ODN did not exert any significant effect (Figures 4C,D), thus suggesting a selective role of TLR8.
0.95 TLR8 with respect to TLR7 (Figure S1 in Supplementary Material).
0.95 TLR7 and TLR8, to the best of our knowledge this is the first demonstration that TLR7/8 ligands can potentiate their activation.
0.85 TLR8 pathway in IEC to the monocyte-mediated inflammatory response, and highlights the capacity of the TLR7/8 agonist R848 to directly enhance the activation of gammadelta T lymphocytes.
0.76 TLR7 and TLR8 to this effect, monocytes were cultured in R848 CM after pre-exposure to phosphorothioate ODN targeting TLR7/8/9 (#2088) or TLR7 (#20958).
0.50 TLR7 and TLR8 to the R848-mediated effect on gammadelta T lymphocytes, these cells were exposed to comparable concentrations of the TLR7 specific ligand CL264.
29103998 0.97 TLR7/8 and TLR8 demonstrated no significant effects on DC expression of costimulatory and maturation markers when compared with Alum (Figure 3).
0.96 TLR7/8 competed with, thereby preventing, the binding of TLR8 agonist to its receptor and reduced its effect on cytokines production because TLR8 agonist is more effective than TLR7/8 when it used alone (Figure 2).
0.94 TLR7/8, and TLR8 had noticeable synergy for induction of cytokines (Figure 4), probably due to sustained signaling provided by dual TLR engagement.
0.92 TLR8 than TLR7, while in another study they expressed lower level of TLR8 than other TLRs except TLR9.
0.81 TLR7 and TLR8 could be explained by the previous observation that IL-12p35 mRNA was up-regulated only by TLR8 but not TLR7.
0.79 TLR7/8 and TLR8 were the most effective adjuvants to mature DCs.
16636134 0.97 TLR7/8 agonist or CpG ODN, but not the TLR8 agonist, are effective adjuvants for enhancing IFN-gamma responses in NHP in vivo.
0.87 TLR8, and TLR9 agonists or ligands based on their ability to selectively activate plasmacytoid (TLR7/8 agonist or CpG ODN), conventional DCs (TLR7/8 or TLR8 agonist) or both (TLR7/8 agonist) in vitro.
0.56 TLR7/8 agonist, but not when the protein was administered with the free TLR7/8, TLR8 agonist, or CpG ODN.
0.56 TLR7/8 agonist but not the TLR8 agonist or CpG ODN had detectable frequencies of cytokine-producing CD45RA-CD95+ CD8+ T cells (IFN-gamma, IL-2, or TNF-alpha) after a single immunization (Fig. 5 A).
18431484 0.97 TLR8 or TLR7/8.
0.96 TLR8 and TLR7/8 agonists, respectively.
0.92 TLR7 triggering speak in favor of additional tissue type specific mechanism(s) beyond NK and CD8+ T-cells which may explain the differences between TLR7 and TLR8 agonists.
0.87 TLR8 or TLR7/8 is reflected by an up-regulation of intracellular IFN-gamma and TNF-alpha and increased cytolytic activity of NK and CD8+ T-cells.
24525049 0.97 TLR7, TLR8, and TLR9).
0.96 TLR7, TLR8, and TLR9 exclusively bind nucleic acids associated with various pathogens and are expressed with endosomal subcellular localization.
0.95 TLR7, and TLR8 when compared to healthy subjects, with TLR3 and TLR9 also displaying a similar trend.
0.90 TLR8 and TLR7 are both X-linked, this may explain their basal levels of up-regulation in SLE patients when compared to age and sex-matched healthy females.
25866635 0.97 TLR7 and TLR8 have been studied on purified CTLs, but only in particular contexts.
0.97 TLR8 engagement, when in the aforementioned publications, both TLR7 and TLR8 pathways were probably stimulated.
0.96 TLR7/8 agonist has first been used as a local treatment in cutaneous square cell carcinoma demonstrating that TLR7/8 engagement on human CD8+ T lymphocytes induced an increased production of granzyme B. However, this study could not demonstrate that this effect was due to a direct engagement of TLR7 or of TLR8 on CD8+ T lymphocytes, or to an indirect effect through APCs or CD4+ T lymphocytes.
0.96 TLR8/7 agonist (data not shown), and a single concentration allowing the highest TLR8 effect without triggering TLR7 pathway was chosen.
29042860 0.97 TLR7, TLR8, IRF5, and STING, as indicated.
0.96 TLR7 ligands on monocytes compared to TLR8 ligands.
0.95 TLR7 knockdown did not significantly affect cytokine induction by either TLR8 ligand or bacteria.
0.93 TLR7, TLR8, IRF5, and STING (stimulator of interferon genes) for cytokine induction in MDM upon infection with viable GBS and E. coli, we performed siRNA-mediated gene silencing, which was efficient for all targets examined (Figure S7A in Supplementary Material) The pU/pLA induced cytokines were strongly reduced after TLR8 silencing (Figure 7).
23166493 0.97 TLR8 and TLR7 both contribute to the recognition of viral ssRNA and are both found in human macrophages.
0.90 TLR7, TLR8 is the predominant signaling pathway through which CL097 inhibits HIV.
0.51 TLR8 and TLR7 in the induction of autophagy in macrophages post-ssRNA40 and CL097 was examined.
25401424 0.97 TLR7 and TLR8 are expressed in human CD4+ T cell subpopulations, but although reports suggest that both TLR7 and TLR8 recognize single-stranded RNA as their natural ligand in APC, no such effect was observed when the TLR8 ligand (ssRNA40 transfected in LyoVec ) was used in these experiments in parallel with TLR7 ligands (Fig. 2f-g).
0.97 TLR7 and TLR8 trigger on CD4+ T cells lead to different phenotypic outcomes.
0.97 TLR7, which would be a more physiological ligand, as these sequences were described in mice and they recognize human TLR8 instead.
28928743 0.97 TLR7 and the closely related TLR8 respond to purine-rich single-stranded ribonucleic acid (ssRNA) to elicit an immune response to pathogens which are recognized in the endosome.
0.93 TLR7 responsiveness, leaving a void in the literature regarding TLR8-specific mechanisms.
0.75 TLR7, TLR8 is more strongly expressed in myeloid cells and to a lesser degree in pDCs.
26274907 0.97 TLR7 and (F) TLR8 and an NF-kappaB-driven reporter SEAP gene were stimulated for 18-24 h with TLR agonists.
0.94 TLR7 and TLR8 transfected cells (Fig 1e and 1f).
17535975 0.96 TLR7 and TLR8 ligands, but not with the vehicle control, led to the intracellular expression of perforin and granzyme B in ~10-15% of these cells (Fig. 5, B and C).
0.96 TLR7 and TLR8 agonists.
0.96 TLR7 and TLR8 agonists.
0.95 TLR7/8-stimulated DCs, we analyzed perforin and granzyme B levels in the supernatants of sorted DCs after TLR7 and TLR8 ligation by ELISA.
0.95 TLR7 and TLR7/8 ligation but not after TLR8 ligation alone or vehicle control (Fig. 6 B), which was consistent with our FACS data described in the previous section.
0.92 TLR7 and TLR8 ligation, we performed cytotoxicity assays with purified peripheral blood-derived mDCs and pDCs as effector cells, and perforin-sensitive K562 (Fig. S2 A, available at http://www.jem.org/cgi/content/full/jem.20070021/DC1) and TRAIL-sensitive Jurkat cell lines as target cells.
0.90 TLR7 and TLR8 ligands, in contrast to the vehicle control (Fig. 6, A and B).
0.82 TLR7 and TLR8 stimulation and of TRAIL on pDCs upon TLR7 stimulation
0.74 TLR7 and TLR8 stimulation.
0.65 TLR7 and TLR8, plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), respectively, are therefore likely candidates for the initiation of the IMQ-induced host defense reaction.
26790609 0.96 TLR7-independent manner (Fig. 2d), as it was not abrogated by the pretreatment of neutrophils with BafilomycinA1 (BafA1), a potent inhibitor of endosomal acidification that is a required condition for efficient TLR7 and TLR8, but not TLR4, signaling (Fig. 2d).
0.96 TLR8 and/or TLR7 agonists.
0.95 TLR7 and its consequent co-activation with TLR8 in response to R848, but, rather, it is substantially mediated by an increased production and release of endogenous TNFalpha.
0.95 TLR7, but not TLR8, mRNA is expressed in human pDCs under resting conditions, TLR7 being upregulated upon pDC incubation with R837 or IFNalpha (Fig. 2b).
0.94 TLR7 (as well as TLR8), and, likely, occurs via other, not yet identified mechanisms.
0.93 TLR7 (left panel) and TLR8 (right panel) mRNA expression either in (a), neutrophils cultured with or without 5 muM R848, 5 and 25 muM R837, in the presence or absence of 1000 U/ml IFNalpha for 20 h, or (b), pDCs cultured for 5 h with or without 5 muM R837 or 1000 U/ml IFNalpha.
0.88 TLR7 and its consequent co-activation with TLR8 in response to R848.
0.83 TLR7 and TLR8 mRNA expression in neutrophils freshly isolated from the peripheral blood of SLE patients with high SLEDAI (n = 6, each symbol identifying a different patient, see Table 1) and healthy donors (n = 10).
0.68 TLR8 with newly induced TLR7.
0.56 TLR7 and its consequent co-activation with TLR8 could occur.
31919342 0.96 TLR8 ligands further increased IL-6 secretion (Fig. 2a, right): at low doses (0.2-1.0 microg/ml), TLR8 and TLR7/8 ligands induced 7 to 30 times higher IL-6 levels relative to the TLR7 ligands R837 and CL264 (Fig. 2a, right).
0.95 TLR7 or TLR8 alone.
0.95 TLR8 and TLR7 stimulation enhanced TCR activation by increasing the level of phosphorylated proteins involved in TCR signaling such as ribosomal protein S6 and, MAPK signaling (p38, ERK1/2) and NFkappaB p65.
0.93 TLR8 and TLR7 augment TCR mediated signaling in CD4+ T cells
0.91 TLR7 or TLR8 ligands.
0.89 TLR7 and induce protective type I interferon responses, myeloid DCs, and macrophages sense endosomal HIV-1 ssRNA by TLR8 but fail to induce a protective immune response (e.g. type I IFNs).
0.75 TLR7 and TLR8.
0.67 TLR7), R848 (TLR7/8), CL75, pU/pLA (TLR8), or CpG (TLR9, 5 muM).
0.54 TLR7 and TLR8 ligands for 0-30 min.
0.52 TLR7 and TLR9 in CD4+ T cells whereas inconsistent results are reported for TLR8: some studies claim that TLR8 is present in T cells, while others show the absence of the receptor.
19630977 0.96 TLR7 and TLR8 activation, we tested 43 of the siRNAs that we had shown to induce IFN production in PBMCs for IFN production in pDCs (TLR7 mediated), and TNFalpha production in PBMCs (TLR8 mediated).
0.93 TLR7 and/or TLR8.
0.83 TLR7 in pDCs leading to IFN production, and/or TLR8 in monocytes leading to IFN and TNFalpha production.
0.82 TLR7 (2 sequences caused more than 50% replicon suppression in pDCs, but secretion of less than 500 pg/mL TNFalpha in PBMCs or TLR8 (8 of 43 caused less than 50% replicon suppression in pDCs, but secretion of more than 500 pg/mL TNFalpha in PBMCs) were identified, there were too few such sequences to draw conclusions about sequence determinants of TLR7 or TLR8 preference.
0.66 TLR7 and TLR8 are both activated by single-stranded RNA.
0.58 TLR7 causing IFNalpha production from pDCs, and A and U rich sequences tend to stimulate TLR8 causing production of both IFNalpha and TNFalpha from monocytes.
0.54 TLR7 and TLR8 activation was confirmed by the respective responses to the TLR7 selective agonist CL087, and the TLR8 selective agonist CL075.
0.52 TLR7 and TLR8 may cause a given immunostimulatory sequence to activate pDCs through TLR7 and/or monocytes through TLR8.
23483986 0.96 TLR8- compared to TLR7-transfected cells at the highest concentration tested.
0.90 TLR8 transfected cells, with VTX-294 also modestly activating TLR7 transfected cells at the highest concentration tested.
0.90 TLR7- or TLR8-transfected cells.
0.77 TLR7 and/or TLR8 adjuvant activity.
0.68 TLR8- than TLR7-transfected HEK cells (EC50, ~50 nM vs. ~5700 nM).
0.67 TLR7 and (D) TLR8 and an NF-kappaB-driven reporter SEAP gene were stimulated for 18-24 h with TLR agonists.
0.59 TLR7 and TLR8.
0.55 TLR7- and TLR8-transfected HEK293 cells.
26351878 0.96 hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8.
0.96 TLR8 agonists, as discussed earlier, evoke the production of Th1-biased cytokines such as TNF-alpha, IL-1, IL-12, IL-18, and IFN-gamma from cells of the monocytoid lineage; pure TLR7-active compounds induce the copious production of IFN-alpha from low-abundance plasmacytoid cells, activate natural killer (NK), and induce mitogenicity in B lymphocytes (manuscript in preparation) and are much weaker in inducing TNF-alpha and IFN-gamma; TLR2 agonists, in contrast, activate neutrophils as evidenced by rapid upregulation of CD11b and p38 MAP kinase activity.
0.95 TLR8 agonists evokes a dominant proinflammatory cytokine profile, including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-12, and IL-18 and appear uniquely potent in enhancing the production of Th1-polarizing cytokines TNF-alpha and IL-12 in APCs.- Our interest in small molecule agonists of TLR8 has led to the exploration of the 2,3-diaminofuro[2,3-c]pyridines, 4-aminofuro[2,3-c]quinolines, 3-alkylquinoline-2-amines, and 1-alkyl-2-aminobenzimidazoles, all of which are pure TLR8 agonists with no detectable activity at TLR7.
0.88 TLR7,- TLR8,- nucleotide oligomerization domain 1 (NOD1), as well as C-C chemokine receptor type 1 (CCR1).
0.60 TLR8 (hTLR8) cocrystallized with two regioisomers of dual TLR7/8-agonistic N1-aminomethylbenzyl-substituted imidazoquinolines (1, 2) showed subtle differences in their interactions in the binding site of hTLR8 (Figure 1).
0.54 TLR7/8-active N1-4-aminomethylbenzyl (1) and N1-3-aminomethylbenzyl (2) substituted imidazoquinolines and pure TLR8-agonistic 3-pentylquinolin-2-amine (3).
28744288 0.96 TLR7, TLR8, and TLR9 signal via the MyD88 pathway, whereas TLR4 can signal via both MyD88-dependent and -independent pathways, we hypothesized that naltrexone may affect the MyD88-dependent signaling pathway and that any effects of naltrexone on IL-6 secretion via TLR4 were compensated for by signaling through the MyD88-independent pathway.
0.96 TLR7, TLR8, and TLR9.
0.91 TLR7, TLR8, and TLR9.
0.90 TLR7, TLR8, and TLR9 but not following stimulation with a TLR4 ligand.
0.90 TLR7 and TLR8 stimulation in a dose-dependent manner, although this did not reach significance (Figure S3 in Supplementary Material).
0.87 TLR7 and TLR8, we sought to determine if naltrexone inhibits IL-6 production after TLR7 (R837 3 microg/ml) or TLR8 (ssRNA 0.5 microg/ml) stimulation.
29155428 0.96 TLR7 and TLR8 with elevated production of various cytokines, contributing to extensive articular destruction and functional decline.
0.89 TLR7 and TLR8 are both expressed on B cells and monocytes while DC plasmacytoids (DCps) express only TLR7 and immature DCs (DC11c+) express only TLR8.
0.81 TLR8 and TLR7 is the first reported in literature, implying that a novel molecular recognition mechanism is involved.
0.79 TLR7 and TLR8 were activated by R848.
0.62 TLR7 and TLR8.
25102141 0.96 TLR7, TLR8, and nucleotide oligomerization domain 1 (NOD1) as well as C-C chemokine receptor type 1 (CCR1).
0.90 TLR7 and mixed TLR8/7 agonists, respectively.
0.85 TLR8 as vaccine adjuvants was, in part, kindled by the necessity of having to first identify chemotypes with pure TLR8 activity, given that the known agonists of TLR8 such as the imidazoquinolines, thiazoloquinolines,- and the 2-aminobenzazepines were found to exhibit mixed TLR7/TLR8-agonism.
0.70 TLR7 activity, and these results confirm absolute specificity of the lead 2-aminobenzimidazole compounds for human TLR8.
30266463 0.96 TLR7, TLR8, TLR9 and TLR10 in the prefrontal cortex (PFC) of two normal control (NC), two depressed suicide (DS), two depressed non-suicide (DNS) and two non-depressed suicide (NDS) subjects.
0.86 TLR7, TLR8, TLR9 and TLR10) in the PFC of DS, depressed non-suicide (DNS), non-depressed suicide (NDS) and NC subjects.
0.79 TLR-7 and TLR-8 require RNA from single stranded viruses.
0.59 TLR7, TLR8, TLR9 and TLR10 and they are expressed in the intracellular compartment such as the endoplasmic reticulum, endosomes, lysosomes, and endolysosomes.
20004021 0.96 TLR7 and TLR8 are phylogenetically closest to each other among all the TLRs, and have high sequence homology.
0.93 TLR8 belongs to a subfamily comprising TLR7, TLR8 and TLR9.
0.70 Toll-like receptor 8 (TLR8) belongs to a subfamily comprising TLR7, TLR8 and TLR9.
24277153 0.96 TLR8 results in a constellation of diseases, strikingly distinct from those related to TLR7 signaling, and points to specific inflammatory diseases that may benefit from inhibition of TLR8 in humans.
0.92 TLR7 is largely coexpressed with TLR9, primarily on B cells and PDCs (plasmacytoid DCs), whereas TLR8 is absent in these cells and abundantly expressed in monocytes, myeloid DCs (mDCs), and neutrophils (see Fig. 9 A), suggesting that activation of human TLR8 by endogenous ligands might lead to a different spectrum of inflammatory disease than the one resulting from activation of TLR7 and TLR9.
28769820 0.96 TLR7, TLR8, and TLR9.
0.84 TLR7 and TLR8 expression is correlated to the aggravated neuroinflammation and poor outcome in acute ischemic stroke patients (Brea et al.,).
31572869 0.96 TLR7 activity and slight enhancement of TLR8 activity.
0.81 hTLR7 in the micromolar range and six oxoadenines (2b, 6a-d, and 8b) activated hTLR8 with EC50 < 50 muM. Oxoadenine 6a was also found to be TLR8-selective.
23526932 0.96 TLR8 dimerization were shaded in cyan, and the corresponding residues in TLR7-LBD were shaded in red.
28592890 0.96 TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 polymorphisms are associated with post-bronchiolitis asthma.
25667415 0.95 TLR7 and TLR8 agonists on monocytes within the context of FcgammaR signaling, we found that TLR8 but not TLR7 agonists elicited the production of Granzyme B. Furthermore, FcgammaR activation also led to Granzyme B production and the simultaneous activation of FcgammaR and TLR8 resulted in additive effects on monocyte Granzyme B production.
0.92 TLR7 and TLR8 agonists elicit differential responses
0.90 TLR8 agonist dosage stemmed from our earlier study with the TLR7/8 dual agonist R-848, where we found that 1 muM was sufficient to elicit changes in FcgammaR. In order to identify the optimal concentration for inducing the expression of Granzyme B we treated monocytes overnight with concentrations from 0.01 to 10.0 muM of TLR8 agonist.
0.87 TLR8-mediated production of Granzyme B was shown to depend on NF-kappaB and IL-12, which would be in agreement with an earlier study showing that TLR8 agonists led to stronger NF-kappaB activation and IL-12 production than TLR7 agonists.
0.85 TLR7, TLR8 and TLR9 agonists.
0.85 TLR8 but not TLR7 agonist treatment (Figure 1A), which we verified at the transcript and protein levels (Figures 1B and 1C).
0.76 TLR7 (3M-055, 1 muM), TLR8 (CL075, 1 muM), TLR9 (CpG, 10 mug/ml), or left untreated.
0.65 TLR8 but not TLR7 agonists could induce this protease.
0.62 TLR7 and TLR8 agonists, microarray analysis showed that many were significantly higher with TLR8 activation.
0.56 TLR7) or VTX-2337 (TLR8), or left untreated (UT).
0.55 TLR7-selective agonist) or with VTX-2337 (TLR8-selective agonist) and compared transcriptional responses to untreated monocytes using microarrays.
0.51 TLR8 agonist treatment induced Perforin-1, we examined our microarray results and saw that Perforin-1 was significantly increased in monocytes treated with TLR8 but not TLR7 agonists (Figure 9A), which we confirmed using qRT-PCR and ELISA (Figures 9B and 9C, respectively).
22243920 0.95 TLR7 and TLR8 expression in monocytes from HIV-infected subjects both in vivo and after in vitro stimulation; however, further studies are needed to elucidate a mechanistic explanation of altered TLR expression in HIV-infected monocytes.
0.94 TLR7 or TLR8 expression and production of these two cytokines but found no correlation (data not shown).
0.94 TLR7 and TLR8 pathway may contribute to the understanding of the immunopathogenesis of HIV infection and may ultimately offer novel targets for immunomodulatory therapy.
0.92 TLR7 is more responsive and hypersensitized to its ligands, while TLR8 expression in monocytes in vitro was stable after stimulation with R-848, which corresponds to the conserved in vivo TLR8 expression in monocytes of subjects from the SPs and HIV chronic stages.
0.88 TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR.
0.85 TLR7 and TLR8 mRNA expression in monocytes differs from the increase in TLR7 and TLR8 mRNA expression as Lester et al. reported in PBMCs, which suggests that monocytes experience a unique change in TLR7/8 expression distinct from other PBMCs.
0.76 TLR7 and TLR8 expression levels in monocytes declined as a function of the severity of HIV infection (i.e. slow progression to chronic HIV infection to AIDS).
0.64 TLR7 and TLR8.
0.55 TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-alpha secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848.
28806745 0.95 TLR7 and TLR8 recognize single-stranded RNA and RNA degradation products from viruses and bacteria, and polymorphisms in TLR7 and 8 have been associated with increased susceptibility to pulmonary tuberculosis.
0.94 TLR7, TLR8, and UNC93B1 in human primary macrophages, achieving an average reduction in mRNA levels of 80% (S6 and S7 Figs).
0.93 TLR7 and TLR8 is not surprising since one would expect most microbes to contain ligands for both receptors.
0.92 TLR7 and 8 recognizes ssRNA in a species-specific manner and we and others have shown that human TLR8 responds to bacterial RNA.
0.88 TLR7/TLR8 recruited to the phagolysosomal compartment
0.84 TLR7, we found both TLR7 and TLR8 to be present in human primary macrophages (here and).
0.81 TLR8 and also TLR7 in phagolysosomes, resulting in recruitment of MyD88, inflammatory signaling and secretion of cytokines.
0.79 TLR7/TLR8, eliciting host responses by recruitment of MyD88 to the phagolysosomal compartment.
0.70 TLR7 and TLR8 are processed at neutral pH and may be present in MavCs, but receptor engagement most likely happens in lysosomal compartments since both TLR7 and 8 respond to ssRNA degradation products (ribonucleosides and oligoribonucleotides) and not intact ssRNA, indicating RNA processing should be required.
32210973 0.95 TLR8 (EC50 = 0.53 muM, Figure 1C and TLR7 (EC50 = 1.12 muM, Figure 1B) while UM-3005 (lipidated at the 7-position) elicited strong NFkB activation through human TLR8 (EC50 = 0.27 muM, Figure 1C) but was much less potent with respect to NFkB activation via human TLR7 (EC50 = 499.2 muM, Figure 1B).
0.95 TLR7 (B; n = 2) or human TLR8 (C; n = 2).
0.91 TLR7/8 amongst other pattern recognition receptors (PRRs), TLR7 and TLR8 are attractive targets for influenza virus vaccine adjuvants.
0.90 TLR7/8 agonists are primarily generated through TLR7 ligation in plasmacytoid dendritic cells (pDCs) and their secretion of IFNalpha while pro-inflammatory responses generated through TLR8 ligation in myeloid dendritic cells [mDCs; ] help shape the resulting innate and adaptive immunity.
0.84 TLR7 (EC50 = 60.5 muM; Figure 1B) and TLR8 (EC50 = 24.6 muM; Figure 1C).
0.83 TLR8-biased compound, elicits the highest concentrations and frequencies of pro-inflammatory and Th1/Th17 biasing cytokines while UM-3003, the least TLR8-biased compound, elicits low concentrations and low frequencies of pro-inflammatory and Th1/Th17 polarizing cytokines but is the most potent inducer of IFNalpha, indicative of TLR7 activity.
0.78 TLR7 (EC50 = 34.7 muM; Figure 1B) and minimally via TLR8 (EC50 = 52.5 muM; Figure 1C).
0.70 TLR7/8 stimulation were of lower frequency, as expected based on the expression of TLR7 but not TLR8 in pDCs (Figure 7, right column).
0.67 TLR7/8 adjuvants, particularly those with a TLR8 bias, demonstrated robust activity in activating human infant APCs and increased neonatal macaque pneumococcus immunogenicity in vivo.
23826189 0.95 TLR7/TLR8 ligands that can mediate direct activation of the immune system in vitro .
0.95 TLR7/Imiquimode, TLR7/TLR8/CL097 and TLR9/CpG. IFN-alpha secretion was determined by cytometric bead array.
0.93 TLR7/TLR8 (CL097) and TLR9 (CpG).
0.87 TLR7 (Imiquimode), TLR7/TLR8 (CL097) and TLR9 (CpG).
0.87 TLR7 (Imiquimode), TLR7/TLR8 (CL097) and TLR9 (CpG).
0.79 TLR7/Imiquimode, TLR7/TLR8/CL097, TLR9/CpG).
0.72 TLR7/8 ligand, that was able to induce an equivalent response between CB and adult blood; this effect was specifically due to TLR8 activation.
0.58 TLR7/Imiquimode, TLR7/TLR8/CL097 and TLR9/CpG. IL-10 secretion was determined by cytometric bead array.
27798161 0.95 TLR7/8 signaling induces the expression of Socs-1 in HEK293 cells, yet these studies did not rule out if this signaling is dependent on TLR7 or TLR8 alone, or an effect of combined TLR7 and TLR8 ligation.
0.92 TLR7 signaling may over-compensate for a loss of TLR8, as the reciprocal has been identified in TLR7 deficiency.
0.92 TLR8, but not on TLR7, which provides ample docking sites for the SH2 regions of SOCS-1 to bind to TLR8.
0.91 TLR8 may function to suppress antiviral immunity through negative regulation of TLR7 signaling.
0.85 TLR8 and not TLR7, in both mock and TLR7 and TLR8 stimulated cells, is yet to be further elucidated.
0.81 TLR8, but not TLR7, suggesting SOCS-1 utilizes TLR8 as an adaptor molecule for its regulation.
0.69 TLR8 signaling negatively regulates TLR7-mediated antiviral immunity
0.57 TLR8 deficient cells (Tlr8-/-) SOCS-1 is not adequately induced, therefore antiviral immunity is minimally inhibited, resulting in increased Isg-56, Irf7, and Tlr7 expression, which ultimately amplifies the TLR7 signaling pathway, while successfully controlling viral load and reducing virus-induced apoptosis.
24146965 0.95 TLR7 and/or TLR8 expressed by monocytes, macrophages, and plasmacytoid dendritic cells (pDCs).
0.94 TLR7 and TLR8) has been reported in keratinocytes.
0.93 TLR7 and TLR8.
0.93 TLR7 and TLR8 by self RNA-antimicrobial peptide complexes provided new insights into the mechanism that provokes the auto-inflammatory responses in psoriasis.
0.82 TLR7 and TLR8, and the action of imiquimod is thought to be mediated by the adenine receptor, not TLR7 or TLR8.
0.63 TLR7 or TLR8 in human keratinocytes, the major cells in the epidermis of the skin, was reported.
26545385 0.95 TLR8-dependent, yet TLR7-independent IL-12 production 27.
0.91 TLR7 and most likely also TLR8 preferentially bind U/G rich viral-, si-, and self-RNA 14, 19, 23, 24, 25.
0.87 TLR8 specificity and lack of TLR7 specificity of the ORNs, bacterial rRNAs, as well as mtRNA (Fig 1C, E, and F) 14.
0.86 TLR7 was weak in Tlr8 -/- cells yet abrogated by TLR7 mRNA expression knockdown (Figs EV2F and G, and EV3A) 19, 23.
0.81 TLR8 and also TLR7 activation, allowed antibiotics to inhibit consequent inflammation.
0.81 TLR8 ligand) BtmtD3_4 to induce substantial IFNalpha production while triggering that of TNF to similar degrees as compared to both infections implicated involvement of further endosomal pattern recognition in bacterial infections such as of tRNA through TLR7 (Figs 4B and EV3C).
19637197 0.95 TLR8 agonist) or R848 (TLR7/8 agonist) in the presence or absence of IC.
0.91 TLR8 but not TLR7 mRNA is expressed in freshly isolated human monocytes.
0.90 TLR8 or TLR7/8 ligand (R848) in a dose-dependent manner.
0.52 TLR8 agonist) or R848 (TLR7/8 agonist) were measured by ELISA (n=3 per treatment group).
27385120 0.95 TLR7 and TLR8 in various antigen presenting cells.
0.94 TLR7, TLR8 or TLR3 were transfected with the pNfity2-luc vector, which includes the luciferase gene under the control of NF-kappaB. Cells were stimulated with selected immunogenic HCV ssRNA sequences (HCVL1, 4 and 8) fused with lipofectamine2000 and the luciferase activity was measured in cell lysates.
0.75 TLR7 and TLR8 can detect single stranded RNA (ssRNA) molecules.
0.56 TLR7 expressing cells, p < 0.0001, and 15-, 6- and 3- fold increase, respectively in TLR8 expressing cells, (p < 0.0001, Fig. 1e).
22617878 0.95 TLR7, TLR8, or both.
0.94 TLR8, while avoiding the type I IFNs response that is typical of TLR7-mediated pDC activation.
25620999 0.94 TLR7 and TLR8 are activated by imidazoquinolines, a family of synthetic, low-molecular-weight compounds with strong antiviral activity, such as imiquimod and resiquimod.
0.94 TLR7 and TLR8 play key roles in sensing viral RNAs and generating antiviral immunity; however, excessive TLR activation by viral infection or by the recognition of self-RNA may generate detrimental immune responses to the host.
0.93 TLR7 and TLR8 pathways in terms of their target cell selectivities and cytokine induction profiles.
0.87 TLR7 and TLR8 are related functionally and detect GU-rich and AU-rich ssRNA sequences from the viral genomes of influenza, HIV-1, vesicular stomatitis virus, coxsackie B virus, coronavirus and flaviviruses (HCV and WNV; reviewed in).
0.76 TLR7-specific agonists were shown to be more effective at inducing type I IFN and IFN-regulated chemokines, while TLR8-specific agonists were more effective at inducing proinflammatory cytokines and chemokines, such as TNF-alpha and IL-12.
0.57 TLR7 is primarily expressed in pDCs and, to some extent, in B cells, monocytes and macrophages, whereas TLR8 is mostly expressed in monocytes, macrophages and myeloid DCs.
25283842 0.94 TLR7/TLR8 agonist, R848, considerably impairs the growth of human AML cells in immunodeficient mice.
26007168 0.93 TLR8 endosomal domain consists of 817 residues for each monomer; residues from 434-458 are missed after the proteolytic cleavage; in TLR7, residues from 436-478 were deleted in each chain during the alignment procedure, as Asn479 is one of the probable sites of cleavage.
0.91 TLR8; in TLR7 the respective residues are Asp555, Gly584, Thr586, Phe349, Tyr356, Gly379, Val381, and Phe408; the modeling of the receptor resulted in 754 residues.
0.86 TLR7 based on a recently published TLR8 template, which includes two molecules of a dual agonist.
0.84 TLR7, but not TLR8.
0.84 TLR7 the C-H-pi interaction between Leu557 and one of the aromatic rings is also present; it is worth highlighting that this residue is not conserved in TLR8 and that Leu557 has been already described as one of the most important residues for the ligand recognition in TLR7.
0.81 TLR7 and TLR8 are depicted in orange for the first monomer and in purple for the second one.
0.71 TLR7, using as template the recently published experimental structure of TLR8.
0.63 TLR7, we propose a model based on the recently disclosed TLR8 dimeric structure as template, which represents the most similar protein in terms of ligands, functions, cellular localization, and sequence similarity.
0.61 Toll-Like Receptor 7 (TLR7) dimer obtained with homology modeling, using the crystallographic structure of TLR8 as template.
0.52 TLR7, TLR8, and TLR9, which are localized at endosomal membranes.
19609346 0.93 TLR7, TLR8, and TLR9, but in a manner different from that of the ubiquitous herpes simplex virus-1, which exerts selective pressure on TLR3.
0.90 TLR7, TLR8 and TLR9.
0.88 TLR7, TLR8 and TLR9 are typically located in intracellular compartments such as the endosomes, whereas
23685782 0.93 TLR7 and TLR8 detect very similar ligands, their expression patterns and the cytokines they induced have been demonstrated to differ.
0.92 TLR7 and TLR8 agonists have been studied in various cancer targets and have shown some promising results.
19426145 0.92 TLR7 is preferentially expressed in plasmacytoid dendritic cells (pDCs), B cells, and likely some monocytes; whereas TLR8 is expressed in myeloid dendritic cells (mDCs), macrophages and neutrophils but not in pDCs.
0.62 TLR7, 3M-002 selectively activates TLR8.
0.54 TLR7 and TLR8 are preferentially expressed in immune cells with distinct patterns of expression.
0.51 TLR7 belongs to a subfamily of the TLRs, comprising TLR3, TLR7, TLR8, and TLR9, which recognizes nucleic acids.
28228119 0.91 TLR7 and TLR8 which are consistently showing a lower level of variation.
0.90 TLR7 and TLR8 which are located in a small region on the X chromosome, both show lower numbers of polymorphisms (1 and 2 polymorphisms, respectively).
0.58 TLR7-TLR8 locus was consistently showing a much lower level of variation.
0.58 TLR7 and TLR8 have been found to be associated with AR in two independent studies.
21533209 0.91 TLR7; p <0.001), ssRNA (TLR8; p<0.001), and CL075 (TLR7/8; p <0.001) all demonstrated age-dependent effects (Table S2A).
0.70 TLR7 and TLR8 selectivity, differences in biochemical structures between ssRNA and the low-molecular weight thiazoloquinolone, CL075 may affect TLR-independent variables (e.g., solubility, protein binding and cell penetration) that may also contribute to distinct bioactivities.
0.55 TLR8 versus TLR7 agonists, significant correlations were noted between TLR agonist-induced mRNA expression of IFNG and IFNgamma protein levels induced by ssRNA (p = 0.005; Figure 8B) and CL075 (p = 0.027; Figure 8C), but not Gardiquimod (p = 0.075; Figure 8A).
28245863 0.90 TLR8 or TLR7 expression was not induced in monocytes latently infected by EBV, as confirmed by the lack of infectious EBV in the cells harboring EBV-p2089 DNA (Fig. 1f and g, and h showing one representative dcSSc patient and HD).
0.53 TLR8 upregulation inhibits the TLR7-IFNalpha response, we found that expression of the BFRF1/lytic gene was associated with a trend of TLR7 downregulation in certain infected HD and dcSSc monocytes (Additional file 1: Figure S8), suggesting that activation of TLR8 may be a new strategy employed by EBV to dampen IFNalpha during lytic replication and control the host innate immune system.
25071732 0.86 TLR7, TLR8, and TLR9 mRNA were less expressed (data not shown).
24782650 0.85 TLR7 and TLR8 are expressed in human lung cancer cells, TLR7 ligand (loxoribine) and TLR8 ligand (PolyU) are able to up-regulate Bcl-2 expression and to promote the survival of lung cancer cells.
0.84 TLR7/TLR8 and Bcl-2/VEGF mRNA level in cervical cancer tissue was analyzed with Pearson method.
0.77 TLR7 or TLR8 agonist, is approved for treatment of genital warts and has been suggested for treatment of other HPV-associated disease including papillomavirus infection.
23123977 0.68 TLR7 and TLR8 pathway, but the IFN-a is not detected after either TLR7 or TLR8 recognition, so the activation process induced by SARS-CoV GU-rich ssRNAs is mainly depended on the MyD88-NF-kb signal pathway but not the MyD88-IRF pathway.
21949866 0.61 TLR7; its agonistic activity at TLR8 appears to be much weaker.



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