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Validated All-in-One™ qPCR Primer for TLR4(NM_138554.2) Search again
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
Summary
The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta, and in myelomonocytic subpopulation of the leukocytes. It has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness. Also, several transcript variants of this gene have been found, but the protein coding potential of most of them is uncertain. [provided by RefSeq].
Gene References into function
- Intestinal epithelial cells express very low levels of Toll-like receptor-4 by a mechanism which protects them against dysregulated proinflammatory signaling in response to Gram-negative commensal bacteria and their products.
- A TLR4 agonist specifically promoted the production of the Th1-inducing cytokine interleukin (IL) 12 p70 and the chemokine interferon-gamma inducible protein (IP)-10.
- downregulation on gingival fibroblasts by Porphyromonas gingivalis lipopolysaccharide
- LPS may activate a mammalian serine protease, which generates a product required for TLR4 signalling
- identification of role in novel signal transduction pathway utilized by exracellular HSP70
- regulation of TLR4 surface expression in human peripheral blood monocytes and B cells by interleukin-2 (IL-2) and IL-4
- stimulation of signal pathway by HSP70
- signaling events by TLR2 and TLR4 agonists are similar but there are distinct differences in the responses elicited by two bacterial products
- sequence polymorphism in the gene causes an endotoxin-hyporesponsive phenotype in humans
- expression regulated by immune-mediated signals in intestinal epithelial cells
- The extracellular, but not cytoplasmic domain of TLR1 inhibits Toll-like receptor 4 signaling in endothelial cells. TLR1 might restrain the dangerous innate response to LPS by binding to TLR4 and preventing the formation of active signaling complexes.
- Though TLR4 binds bacterial lipopolysaccharides, it had no role in binding non-lipopolysaccharide components from C. pneumoniae.
- interferon-gamma augmented mRNA and surface expression of TLR4 in monocytes and macrophages
- involvement in cell activation by mannuronic acid polymers
- bacterium-induced CXCL10 secretion by osteoblast can be mediated in part through toll-like receptor 4
- The Asp299Gly TLR4 polymorphism is associated with a decreased risk of atherosclerosis.
- Hypoxia decreases TLR4 expression in endothelial cells and this change is mediated by mitochondrial ROS leading to attenuation of AP-1 transcriptional activity.
- Data show that the TLR4-mediated LPS response in bladder epithelial cells also uses the co-receptor CD14 for efficient LPS signalling.
- According to the present results an allelic variation in the TLR4 receptor was associated with increased risk of premature birth.
- Susceptibility of human dendritic cells (DCs) to measles virus (MV) depends on their activation stages in conjunction with the level of CDw150: role of Toll stimulators in DC maturation and MV amplification
- Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex
- Although expression levels of TLR4 mRNA and protein are normal in lipopolysaccharide (LPS)-tolerant monocytes, association of TLR4 with MyD88 is inhibited by LPS restimulation.
- We conclude that the CARD15 mutation and hyporesponsive TLR4 allele do not contribute to ethnic variation in the incidence of PPROM.
- role of polymorphism in susceptibility to Candida albicans infection
- Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes.
- lipopolysaccharide may induce proliferation of periodontal epithelial cells by upregulating keratinocyte growth factor 1 expression via the CD14 and Toll-like receptor signaling pathway
- LPS-induced NF-kappaB activation and IL-8 gene expression use a signaling pathway requiring protein tyrosine kinase and that such regulation may occur through tyrosine phosphorylation of TLR4.
- TLR2 and TLR4 mRNA were significantly up-regulated by IL-10 in monocyte cells that were adherent compared to those nonadherent.
- participates in the innate immune response to stimulation by bacterial products in periodontal tissues
- Expressed in immortalized human liver cell lines
- These data indicate that Toll-like receptor 4 modulation of polymorphonuclear leukocyte (PMN) surface chemokine receptor expression is a critical determinant of PMN migration.
- innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by Gram-positive pathogens. while TLR-4 and MD-2 are not involved
- findings indicate that, although the gastric epithelium is important in directing the immune response against H. pylori infections, the response is independent of TLR4
- Mutations in the gene for toll-like receptor 4 and multiple sclerosis
- Review. TLR4 signaling is intimately involved in anti-cancer immunity induced by immunopotentiators. Our clinical examination in oral cancer patients also suggests the requirement of both TLR4 and MD-2 in the OK-432-induced anti-cancer host response.
- human activated hepatic stellate cells utilize components of TLR4 signal transduction cascade to stimulate NF-kappaB and JNK and up-regulate chemokines and adhesion molecules.
- TLR4 activation of NFkappaB requires Bruton's tyrosine kinase
- Assay of locus-specific genetic load implicates mutations in this receptor in meningococcal susceptibility.
- First comparative investigation in highly purified, monocyte-depleted neutrophil populations shows a distinct and separate role for TLR4, compared with TLR2, in neutrophil responses and neutrophil survival.
- TLR4 is able to undergo multiple glycosylations without MD-2 but that the specific glycosylation essential for cell surface expression requires the presence of MD-2.
- Among symptomatic men with documented coronary artery disease, the TLR4 Asp299Gly polymorphism was associated with the risk of cardiovascular events; carriers of the allele had significantly more benefit from pravastatin
- Polymorphism is associated with systemic inflammatory response syndrome.
- TLR4 polymorphism contributes to the development acute rejection after lung transplantation.
- TLR4 has a role in inducing IL8 transcription in a pathway involving oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine
- TLR4 has a role in upregulating IL-8 through neutrophil elastase
- Data show that monocytes from individuals heterozygous for both mutations in the toll-like receptor 4 gene exhibit no deficit in recognition of lipopolysaccharides from different species of bacteria.
- Data show that Toll-like receptors TLR2 and TLR4 were expressed on dendritic cells, whereas only TLR2 was weakly detected on Langerhans cells.
- there may be a resistive exercise training-induced reduction in TLR4/CD14 expression in older women.
- TLR-4 polymorphism does not appear to influence susceptibility to rheumatoid arthritis.
- a functional Toll-like receptor 4 (TLR4) was expressed on human mast cells when it was up-regulated by interferon gamma (IFN-gamma).
- saturated and polyunsaturated fatty acids reciprocally modulate the activation of TLR4 and its downstream signaling pathways involving MyD88/IRAK/TRAF6 and PI3K/AKT.
- signaling pathways involved in NF-kappa B activation by TLR4 signaling in microvascular endothelial cells
- The TLR4 gene G299/I399 polymorphisms were associated with a modified response to endotoxin in asthma
- Down-regulation of TLR-4 by TNF-alpha is associated with LPS hyporeactivity for NF-kappaB formation, whereas upregulation of TLR-4 via IL-6 can increase the responsiveness of mononuclear phagocytes
- Results show that the surface receptors TLR2/4 and CD14 are essential for in vitro cellular activation induced by Neisseria meningitidis lipopolysaccharide-containing outer membrane vesicles and purified lipopolysaccharides.
- The findings of this study do not support the hypothesis that the toll-like receptor 4 (TLR4) Asp299Gly polymorphism influences predisposition to and progression of coronary artery disease.
- Toll-like receptor-4 aggregation and signal transduction are affected by lipopolysaccharide binding to MD-2
- data demonstrate that the heterozygous Asp299Gly polymorphism does not exhibit a functional defect in cytokine release after the stimulation of blood monocytes
- LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF.
- lipopolysaccharide-TLR4-mediated activation of IFN-beta requires the adapter complex of TICAM-2 and TICAM-1
- TLR4-mediated activation of the interferon-sensitive response element has an absolute requirement for NFKBp65, whereas the TLR3-induced ISRE response is NFKB-independent
- The Asp299Gly polymorphism provides evidence of an association of the TLR4 receptor and acute coronary syndromes.
- TLR4 has a role in an LPS-induced inflammatory response as demonstrated by increased mitogen-activated protein (MAP) kinase activity, IL-8 production, and tumor necrosis factor alpha production
- The endotoxin receptor TLR4 polymorphism is not associated with diabetes or components of the metabolic syndrome
- When the effect of lipopolysaccharide contamination is abrogated, Hsp65 is unable to activate TLR4 in the presence of CD14 and MD2.
- TLR4 is a key element in the response of pulmonary epithelial cells to Gram-negative bacteria. The intracellular localization of TLR4 in lung epithelia plays an important role in the prevention of the development of chronic inflammatory disease.
- The single-nucleotide polymorphisms at position +896 or +1196 in the TLR-4 gene is associated with systemic inflammatory hyporesponsiveness to inhaled lipopolysaccharide.
- P. gingivalis LPS-dependent antagonism of E. coli LPS in human endothelial cells likely involves the ability of P. gingivalis LPS to directly compete with E. coli LPS at the TLR4 signaling complex.
- Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with reduced prevalence of diabetic neuropathy in type 2, but not in type 1, diabetes.
- TLR4 intracellular domains have an important role in receptor dimerization
- downregulated by Ehrlichia chaffeensis infection in monocytes
- expression of CCL21, and TLRs 2 and 4 is predominantly induced in the peripheral lymphatic endothelium of the small intestinal microcirculation
- TLR4 has a role in hyaluronan-stimulated endothelial recognition of injury
- in this model of natural LPS release, the variation between individuals in TNF-alpha release can only modestly be determined by genetic background (tumor necrosis factor -alpha promoter, Nod2 and TLR4) of the individual
- Association between rheumatoid arthritis disease susceptibility and functional TLR-4 variant. TLR-4 polymorphism also associated with disease activity at baseline but not with disease severity or outcome.
- Reactive oxygen species regulate immune signaling through TLR4 via their effects on NF-kappa B activation
- Expression of toll-like receptor 4 and immune response in innate immunity may be altered after surgical insults.
- primary ATII cells express mRNA and protein for both TLR-2 and TLR-4, which can be modulated by incubation with lipopolysaccharide and tumor necrosis factor
- Involvement of CD14/TLR4, CR3, and phosphatidylinositol 3-kinase in the degradation of IL-1 receptor-associated kinase in response to LPS.
- Comparison of the genotypes of 242 patients with Guillain-Barre syndrome (GBS) and 210 healthy subjects shows that polymorphisms in Toll-like receptor 4 do not confer susceptibility to GBS and are not associated with Campylobacter jejuni infection.
- TLR4 is not only located intracellularly but also functions intracellularly in human coronary artery & umbilical vein endothelial cells, thus internalization of LPS is required for its activation.
- TLR4 mediates antitumor immunity induced by the plant-derived (Aeginetia indica L) protein AILb-A.
- upregulation of TLR expression during differentiation in keratinocytes could be a part of the differentiation process of keratinocytes and could have biological significance in protecting skin against microbes.
- detected in epithelial cells lining the entire urinary tract and in the renal tubular epithelium in response to Escherichia coli infections
- Toll-like receptor 4 is activated by MD-2 and lipopolysaccharide in inflammation
- activation of Rac1 leads to HIV-LTR trans-activation, mediated through TIRAP. Rac1 and TIRAP are important in TLR4 activation of HIV replication
- Hepatocytes utilize components of TLR4 signal transduction pathways in response to lipopolysaccharide.
- inhibition of TLR4-mediated activation of NF-kappa B by MalE190A
- The Asp299Gly TLR4-allele might have a protective role in carotid atherosclerosis, but not in cerebral ischemia.
- TLR4 of retinal pigment epithelial cells participates in transmembrane signaling events that contribute to the recognition and clearance of effete photoreceptor outer segments, a process central to the maintenance of normal vision.
- Toll-like receptor 4 (TLR4) was expressed in the human adrenocortical cell line NCI-H295. Immunohistochemical analysis of normal human adrenal glands revealed TLR4 expression in the adrenal cortex, but not in the adrenal medulla.
- The presence of multiple lipid A species in Porphyromonas gingivalis lipopolysaccharide contributes to cell activation through both TLR2 and TLR4.
- Results show that the N-terminal region of toll-like receptor 4 is essential for association with MD-2, which is required for the cell surface expression and hence the responsiveness to lipopolysaccharide.
- pancreatic elastase-induced proinflammatory effects are mediated by TLR4 and NF-kappaB in human myeloid cells
- Direct interaction of TLR4 with NADPH oxidase 4/NOX4 is involved in lipopolysaccharide-mediated generation of reactive oxygen species and NF-kappa B activation in HEK293T cells.
- The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4)and decreased LPS-induced IL-12(p70) and IL-10 responses.
- The TLR4 896 A > G polymorphism contributes to inter-individual differences in the vaginal immune defense against G. vaginalis and anaerobic Gram-negative rods.
- TLRs are differentially expressed in distinct compartments of the female reproductive tract
- Coxsackievirus B4 triggers cytokine production through a TLR4-dependent pathway in pancreatic cells.
- The mutants of TLR4 did not inhibit H. pylori-induced COX-2 promoter activity. in gastric mucosa.
- the endotoxin tolerance seen in patients with sepsis does not depend solely on TLR-2 or TLR-4 expression
- interleukin-1beta has roles in direct and toll-like receptor 4-mediated neutrophil activation and survival
- TLR4 antibody blockage in human macrophages demonstrates that TLR4 is a putative receptor of extract of Ganoderma lucidum (Reishi) polysaccharides and mediates the consequent immunomodulating events associated with IL-1 gene expression.
- Prevalence of the TLR4 genotype may have an association with acute myocardial infarction and with longevity.
- The extracellular TLR4-MD-2 complex, but not TLR4 alone, can bind lipopolysaccharide (LPS). Extracellular TLR4 domain (residues Glu24-Lys631) enables MD-2 binding and LPS recognition to TLR4.
- The Toll-like receptor 4 Asp299Gly gene polymorphism was not associated with risk of incident myocardial infarction or stroke in a large prospective study of US men.
- blockage of TLR-4 activation by EGCG resulted in inactivation of extracellular signal response kinase 1/2 and of nuclear factor-kappaB, the downstream molecules of TLR-4 signaling induced by H. pylori
- Neutrophil elastase, MIP-2, and TLR-4 have roles in progression of human sepsis and murine peritonitis
- TGF-beta1 can specifically interfere with TLR2, -4, or -5 ligand-induced responses involving the adaptor molecule MyD88 (myeloid differentiation factor 88) but not the TRAM/TRIF signaling pathway
- The TLR4 299Gly allele was associated with reduced CRP levels and, in parallel, a decreased risk of angiographic CAD and clinical diabetes
- Pattern recognition of bacterial superantigens by MHC class II receptors may exacerbate the proinflammatory response of monocytes to Gram-negative infection or endotoxin by up-regulation of TLR4.
- co-existence of a mutation in either the TLR4 or CD14 gene, and in NOD2/CARD15 is associated with an increased susceptibility to developing Crohn disease compared to ulcerative colitis
- evidence that HPV-VLP signal dendritic cells through a pathway involving proteoglycan receptors, TLR4 and NF-kappaB
- the function of CaMK II is essential for PAF-induced macrophage priming, while CaMK IV is not specific for priming by PAF and appears to have a direct link in TLR4-mediated events
- CXCR4 could exert local control of TLR4 and suggest the possibility of new therapeutic approaches to suppression of TLR4 function
- These results clearly demonstrate that the amino-terminal TLR4 region of Glu(24)-Pro(34) is critical for MD-2 binding and LPS signaling.
- TLR4 may play an important role in modulation of immunological tolerance in the lower parts of the female reproductive tract, and in host defence against ascending infection.
- Sampling analysis in Han population of Chongqing showed that the two highly distributed SNPs of TLR4 were common in Chinese population and could be used for genetic marker of TLR4 gene.
- TLR4 SNPs are associated with resistance to Legionnaires' disease.
- Engagement of TLR4 mediates deactivation of human monocytes in the presence of tumor cells, an effect apparently involved in IL-1 receptor associated kinase-M (IRAK-M) up-regulation.
- We further confirmed that the No. 9 peptide could bind to TLR4 extracellular domain, but the No. 24 peptide could not, suggesting that two peptides were identified as antagonists of TLR4, which inhibited the effects of endotoxin in vitro.
- lipopolysaccharides from some Helicobacter pylori strains are able to antagonize TLR4
- BCG induced transcription and secretion of the chemokine CXCL8, by signalling through Toll-like receptors TLR2 and TLR4, in conjunction with myeloid differentiation factor 88 (MyD88)in neutrophils
- Although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.
- Mastoparan, a G protein agonist peptide,preferentially targets the TLR4 pathway over the TLR2 pathway, confirming the importance of heterotrimeric G proteins in TLR4-mediated responses
- The TLR4 expression was analyzed after the stimulation of JAR cells with different TLR ligands.
- Data suggest that, during Gram-negative bacteria-induced infections or inflammatory processes, LPS could affect pituitary tumour pathophysiology and progression in the subset of Tlr4-expressing pituitary adenomas.
- HSP65 and HSP70 from Mycobacterium tuberculosis signal via TLR4 in human cells
- examination of a variant as candidate gene for age related macular degeneration susceptibility
- TLR4 signaling effects the induction of cell death by secreted Helicobacter pylori antigen HP0175 in human gastric epithelial cell line AGS.
- activation of TLR4-MyD88-dependent and -independent signaling pathways by endotoxins determined by structure of the endotoxin
- RP105 regulated TLR4 signaling in dendritic cells
- TLR4 signaling promotes a proinflammatory phenotype in vascular smooth muscle cells
- variation in the TLR4 gene contributes to inter-individual variability in susceptibility to coronary ischaemic events, and TLR4 genotype and statin treatment may have a synergistic effect
- expression down-regulated in Helicobacter pylori infected monocytes by clarithromycin
- SIGIRR inhibits IL-1R and TLR4-mediated signaling through different mechanisms
- minimized expression of TLR4 contributes to the susceptibility of very low birth weight infants to infections with Gram-negative bacteria due to the lack of cytokines to boost initial immune response
- unstable angina and myocardial infarction are associated with enhanced expression and signaling events downstream of hTLR4 in circulating monocytes
- TLR4 is associated with both Crohn's disease and ulcerative colitis; Asp299Gly and Thr399Ile variants do not show an association with Crohn's disease, ulcerative colitis, or inflammatory bowel disease and are likely not the causal polymorphisms
- results indicate that Entamoeba histolytica lipopeptidophosphoglycan initiates an innate immune response by interacting with TLR2 and TLR4
- Data possibly implicate TLR4 as an important genetic factor for stroke in ethnic Chinese populations despite the rarity of the Asp299Gly polymorphism
- phenomenon as shown by experiments using different toll-like receptor-agonists in interleukin 10(-/-) macrophages
- first study to demonstrate that even homozygosity for the Asp299Gly mutation does not confer hyporesponsiveness to stimulation with TLR4 stimuli
- An Asp299Gly polymorphism in the TLR-4 receptor has no clinical relevance in multiple sclerosis patients with different TLR-4 genotypes.
- TLR3 and TLR4 signal primarily through NF-kappaB to enhance transcription of pIgR mRNA.
- TLR4 Asp299Gly polymorphism seems to be a minor risk factor for CD in the population studied. TLR4 and CARD15/NOD2 mutations may contribute to the development of distinct CD phenotypes.
- Diminished expression and function of TLR4 is a likely consequence of chronic filarial antigen stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in lymphatic filariasis
- Toll-like receptor 4 (TLR4) is expressed in bile duct epithelial cells and periportal hepatocytes in primary biliary cirrhosis (PBC) livers, suggesting the possible involvement of bacterial pathogens and TLR4 in the inflammatory processes of PBC.
- a functional Toll-like receptor 4 polymorphism may have a role in susceptibility to gastric mucosa-associated lymphoid tissue lymphoma
- first study describing TLR expression on tumor cells of gastric carcinoma and its precursor lesions
- signaling pathways activated by LPS and its receptor TLR4 and TNFalpha have roles in septic shock [review]
- Finds that TLR-4 polymorphisms influence regulators of the inflammation induced by endotoxin in organic dusts
- The up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients with symptomatic allergic rhinitis supports the idea of a role for Toll-like receptors in allergic airway inflammation.
- TLR-4 protein expression is increased in interstitial trophoblasts of paitents with preeclampsia.
- Our data further support a role for innate immunity in neurodegeneration and give the first evidence that the TLR4 Asp299Gly variant may be protective toward the development of LOAD.
- Our results suggest that overexpression of TLR2 and TLR4 in CHO cells sensitizes the cells to serum deprivation-induced apoptosis and that the mechanisms are involved in the death receptor-mediated signaling pathway.
- In females the TLR4 and IL4 genes show an epistatic effect on the risk of asthma.
- This data defines an additional role for TLR4 in the host defense in the lung.
- the synergistic effect of LPS and PepG on cytokine release is preceded by a reciprocal upregulation of TLR2 and TLR4 by both Staphylococcus aureus cell wall components
- Polymorphisms in the TLR4 gene may be associated with milder forms of disease in atopic asthmatics in the Turkish children studied.
- first direct evidence that HMGB1 can interact with both TLR2 and TLR4 and also supply an explanation for the ability of HMGB1 to induce cellular activation and generate inflammatory responses that are similar to those initiated by LPS
- TLR2 and TLR4 agonists have a significant role in diseases such as atherosclerosis and DIC, but our research suggests that this is through a mechanism other than direct platelet activation or by modification of platelet responses to other agonists.
- Maternal allergy status may affect allergic risk in offspring through a decreased expression of fetal TLR4.
- A PRotein Associated with Tlr4 (PRAT4B), regulates cell surface expression of TLR4. PRAT4B has a signal peptide followed by a mature peptide. PRAT4B is associated with the hypoglycosylated, immature form of TLR4 but not with MD-2 or TLR2.
- the subcellular localization of TLR-4 in term placenta is preferentially in the maternal facing plasma membrane compared to basal membrane .
- A study evaluating the role of polymorphic alleles of TLR4 gene in susceptibility to brucellosis is presented.
- Single Nucleotide Polymorphisms in toll-like receptor 4 is associated with prostate cancer
- TLR4-mediated responses to malaria in vivo and TLR-4 polymorphisms are associated with disease manifestation.
- Reduced TXA(2) biosynthesis may contribute to the protective cardiovascular phenotype of TLR4 polymorphisms.
- TLR-4 gene mutations increased risk for severe acute GVHD
- Mal phosphorylation has an effect on tyrosine during signaling by TLR2 and TLR4 and Btk is the kinase involved
- High-dose simvastatin pretreatment blunted TLR4 expression on monocytes in a human endotoxemia model on a posttranscriptional level.
- the TLR4 gene promoter region point mutations do not appear to play a role in myocardial infarction
- Both hypoxia and heat shock prevented the lipopolysaccharide-induced increase in adult CD11b although it was unaltered in neonates.
- data provide evidence for a common requirement for Bruton's tyrosine kinase in TLR2- and TLR4-mediated induction of two important proinflammatory cytokines, TNF and IL-1beta
- concludes that Toll-like receptor 4 is not expressed in epithelial layer, but rather on smooth muscle and myenteric plexus cells and that expression is functional
- Ciprofloaxin suppressed the expression of toll-like receptor-4 induced by lipopolysaccharides in monocytes.
- Activation of innate immunity through TLR4 in the donor kidney contributes to the development of acute rejection after renal transplantation.
- These data support the novel concept that TLR4 activation in ASM elicits changes in ASM function that are regulated by opposing effects of MAPK signaling.
- role for lung epithelial TLR4 as a modulator of cellular apoptosis in response to oxidant stress
- The myristoylation of TRAM targets it to the plasma membrane, where it is essential for LPS responses through the TLR4 signal transduction pathway.
- TLR4 Asp299Gly/Thr399Ile polymorphisms are associated with an increased susceptibility to Candida bloodstream infections, and an increased production of IL-10 is probably involved in this effect.
- In human intrahepatic biliary epithelial cells, at least TLR2 and 4 are capable of mediating innate immune system function in vitro, suggesting the involvement of TLRs in the development of chronic inflammatory cholangiopathies.
- Taken together, these results suggest that TLR4 may provide an explanation for the pathological ability of gangliosides to cause inflammatory conditions in the brain.
- findings indicated that the polymorphism of CD14 but not TLR4 Asp299Gly mutation was associated with Chinese patients with colorectal cancer
- Elevated circulating levels of HSP70 may be involved in TLR4 signal-mediated immune response and the progression of heart failure after acute myocardial infarction
- Cyanobacterial product is a potent competitive inhibitor of lipopolysaccharides in vitro and in vivo and reveal the requirement of sustained TLR4 stimulation for induction of cytokine genes in human dendritic cells.
- we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection with live pathogens may lead to activation of PRR not targeted by inactivated bacteria.
- The capacity of monocytes to synthesize proinflammatory cytokines was significantly reduced in infection prone chronic renal insufficiency patients, and this may possibly be due to the reduced monocyte expression of TLR4
- Pathogen recognition receptor TLR4 is involved in activation of immature monocyte-derived dendritic cells by the envelope protein surface unit (ENV-SU) of multiple sclerosis-associated retroviral element (MSRV) of human endogenous retrovirus.
- SP-A bound to sTLR4 and MD-2 in a Ca2+-dependent manner, and involved the carbohydrate recognition domain (CRD) in the binding. SP-A avidly bound to the deglycosylated forms of sTLR4 and MD-2, suggesting a protein/protein interaction.
- TLR2 and TLR4 ligand interaction with the N-terminal domain of Gp96 amplifies innate and adaptive immune response
- This study demonstrates that TLR4 assembly and activation following LPS exposure require the production of ceramide by PC-PLC, which appears to be CD14-dependent.
- TLR4 and TLR9 polymorphisms increased the risk of low birth weight in infants; polymorphisms of TLR4 increased the risk of maternal anemia.
- A structural ectodomain model of TLR4 that accounts for the diminished responsiveness of mutant TLR4 polymorphisms to structurally unrelated TLR4 agonists is proposed.
- TLR4 has a heterozygous Thr 135 Ala polymorphism at its leucine-rich repeat (LRR)in patients with poorly-differentiated gastric adenocarcinomas.
- Toll-like receptors (TLRs) are increased in osteoarthritic (OA) cartilage lesions. TLR-2 and TLR-4 ligands strongly induce catabolic responses in chondrocytes.
- TLR4 mediates chlamydial heat shock protein 60-induced apoptosis in primary human trophoblasts and placental fibroblasts, providing a novel mechanism of pathogenesis for poor fertility and pregnancy outcome in women with persistent chlamydia infection.
- The moderate systemic inflammatory response produced by intravenous LPS administration in human subjects is not modulated by the presence of heterozygous mutations in the hTLR4 gene.
- no effect on clinical phenotype was seen for TLR4 genotype in cystic fibrosis in the 100 subjects studied
- HSP60 uses TLR2 as well as TLR4 to cause its mitogenic effect on venous smooth muscle cells
- data suggest that there is a differential usage of TLR2 and TLR4 in HMGB1 signaling in primary cells and in established cell lines.
- we report an association of microsatelite GT polymorphisms of TLR2 gene and Asp299Gly polymorphism of the TLR4 gene with sporadic colorectal cancer among Croatians.
- Vasoactive Intestinal Peptide decreases lipopolysaccharide (LPS) and TNF-alpha-induced expression of TLR4 and its correlation with the production of CCL2 and CXCL8 chemokines in human synovial fibroblasts
- A mutation in TLR4 is associated with sarcoidosis.
- Activation of TLR4 mediates chemokine release in airway smooth muscle cells isolated from human lung.
- increased monocyte expression of TLR2, but not of TLR4, correlates significantly with both increased circulating TNF-alpha levels and hepatic necroinflammatory activity in this disorder
- 11350C variant suggested that the TLR4 3'-UTR is a potent regulator of gene expression and downregulation may involve a high risk of nasopharyngeal carcinoma.
- VIP decreased monocyte differentiation to macrophages induced by LPS from either species and also reduced overall TLR2 and TLR4 expression in these cells.
- findings demonstrated that TLR2 and TLR4 were expressed at relatively high levels on the surface of human adipose cells
- Activation of NADPH oxidase and MAPK-signaling pathway contribute to HuR-mediated stabilization of TLR4 mRNA induced by LPS in human aortic smooth muscle cells (HASMCs). Stimulation of HASMCs with LPS increased the cytosolic HuR level in vitro.
- Findings suggest NADPH oxidase activation, mRNA stabilization, and MAPK signaling pathways play critical roles in LPS-enhanced TLR4 expression in human aortic smooth muscle cells, which contributes to vascular inflammation and cardiovascular disorders.
- RANTES down-regulates TLR4 ligation-induced IL-6 and TNF-alpha secretion by enhancing IL-10 production in PB monocytes.
- TLR2 activation was observed with a high bacterial inoculum, and in epithelial cells expressing TLR2 but not TLR4. Enterobacteria-activated leukocytes and endothelial cells in a TLR4/MD-2-dependent
- Translocation to the basal membrane may decrease lipopolysaccharide signaling in an infection, but allow the amniotic epithelium to remain competent to invasive or intracellular bacteria.
- TLR4 region Glu(24)-Lys(47) is a site for MD-2 binding and that Cys(29) and Cys(40) within this region are critical residues for MD-2 binding and LPS signaling
- Human retinal pigment epithelial TLR4 participates in photoreceptor outer segment membrane recognition, oxidant production, LPS recognition, and cytokine production. Potential involvement in retinal degeneratiion and inflammation.
- no association of CD14 or TLR4 polymorphisms with H. pylori-related gastric malignancy.
- In the TLR4 gene, Asp 299Gly polymorphism did not reach to a statistically significant value in rheumatic heart disease patients
- The role of TLR2 and TLR4 in bacterial infections and their potential role as therapeutic targets are reviewed.
- The role of TLR4 in the inflammatory processes associated with endotoxin-induced vascular damage and cardiovascular disease is reviewed.
- The binding of endotoxin.MD-2 to the TLR4 ectodomain (TLR4ECD) and transfer of endotoxin from CD14 to MD-2/TLR4ECD were demonstrated
- There is no association of TLR4 polymorphism with diabetes mellitus, type 1 in the Basque population.
- a modest association between 2 functional variants of TLR4 and ankylosing spondylitis in the Newfoundland population was observed
- Review. Toll Like Receptor-4, responsible for the recognition of bacterial motif as lipopolysaccharide, is implicated in PPARgamma regulation and its anti-inflammatory properties.
- Human NB-1 neuroblastoma cells expressed intracellular form of TLR4, but not the cell surface form; unresponsiveness of these cells to lipopolysaccharide might be due to intracellular localization of TLR4
- The intersubject variability of F3 mRNA production in monocytes and its relation with TLR4 was studied.
- These data suggest that Toll-like receptor 2 and 4 expression correlates with the extent and severity of coronary artery disease.
- Plays a role in mediating the effects of E. coli maltose-binding protein in dendritic cells.
- study shows tyrosine kinase Syk constitutively associates with TLR4 in THP-1 cells; findings implicate Syk as a novel modulator of LPS-mediated TLR4 response in monocytic cells & shed insight on the kinetics of early complex formation upon LPS engagement
- Development of skin lesions in mycosis fungoides appears associated with an increase of TLR4 expression by keratinocytes in cutaneous lesions.
- In a genotypic analysis of Koreans with systemic autoimmune diseases, we found Asp299Gly and Thr399Ile polymorphisms of Toll-like receptor 4.
- REVIEW: EtOH acts by altering the LPS-induced redistribution of components of the TLR4 complex within the lipid raft and this is related to changes in actin cytoskeleton rearrangement, receptor clustering, and subsequent signaling.
- Haplotypes analysis of the two TLR4 polymorphisms by three independent programs revealed association of haplotypes with severe respiratory syncytial virus infection.
- expression levels of TLR2, TLR3, TLR4 & TLR9 in endometrium varied in a similar pattern during the menstrual cycle; levels were high in perimenstrual period & low in periovulatory period
- Expression of maturation markers was diminished with increasing zoledronic acid levels upon lipopolysaccharide activation.
- Interferon-gamma and bacterial lipopolysaccharide act synergistically on human neutrophils enhancing interleukin-8, interleukin-1beta, tumor necrosis factor-alpha, and interleukin-12 p70 secretion and phagocytosis via upregulation of toll-like receptor 4
- The Asp299Gly TLR4 gene polymorphism is associated with a decreased risk of aggressive periodontitis but not chronic periodontitis.
- Constitutive cytokine secretion leads to activation of STATs in Niemann-Pick disease type C fibroblasts, and this secretion is partly caused by endosomal accumulation of TLR4.
- relationship between the carrier status of HSPA1B (1267)G and TLR4 (896)G alleles and the development of recurrent UTI in childhood independently of other renal abnormalities
- TLR4 expressed on human lung cancer cells is functionally active, and may play important roles in promoting immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance
- no evidence for genetic variation in TLR4 being risk factors for increased carotid artery intima-media thickness either directly or through interaction with proinflammatory risk factors
- LPS can up-regulate TLR4 mRNA and protein expression in human aortic smooth muscle cells in dose- and time-dependent manner.
- The incidence of polymorphism in kidney donors or recipients were not associated with different renal graft outcomes.
- TLR4-mediated responses to malaria in vivo and TLR-4 polymorphisms to be associated with disease manifestation
- Assembly and activation of the TLR4 receptor following LPS binding to CD14 requires the production of ceramide by acid sphingomyelinase.
- Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood.
- There is a selective perturbation in the expression and function of TLR4, which could be consistent with a state of endotoxin tolerance, in patients with active acute anterior uveitis
- TLR-2 and TLR-4 expression on monocytes was investigated by flow cytometry in the following groups of subjects: healthy controls, patients on hemodialysis, patients with end-stage renal disease (ESRD) and patients on peritoneal dialysis (PD).
- Intestinal enteroendocrine cells express TLRs which may be involved in innate immune responses.
- Butyrate produced by C. butyricum TO-A downregulates TLR4 mRNA level in human colonic epithelial cells.
- Toll-like receptor 4 Asp299Gly polymorphism is associated with the infection of pancreatic necrosis in acute pancreatitis.
- Although bacterial components increased TLR4 mRNA, only lipopolysaccharide (LPS) augmented the TLR4 protein expression
- The Asp299Gly TLR4 polymorphism does not alter receptor function and does not influence the risk of severe respiratory syncytial virus infection.
- in addition to the classical NF-kappaB-associated pathway, TLR4 triggers a distinct and more rapid signaling response in bladder cells exposed to lipopolysaccharide
- These results rule out a noteworthy influence of the TLR4 polymorphism upon human longevity or MI in German men.
- Downstream of TLR4 in human neutrophils there exists an unbalanced activation of the "MyD88-dependent" and the "MyD88-independent" pathways, whose mechanisms governing lipopolysaccharide responsiveness are regulated in a cell-specific manner.
- results suggest that the TLR4/11367 polymorphism may be a functional single nucleotide polymorphism, which could attenuate the LPS-induced transmembrane signaling through alteration of post-transcriptional regulation of 3'UTR & target gene expression
- in vitro data indicate an anti-anabolic effect of TLR-4 in articular chondrocytes that may hamper cartilage repair in various joint diseases
- analysis offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to inflammatory bowel diseases
- Reduced expression of TLR4 is associated with the metastatic status of colorectal cancer.
- TLR4 gene polymoprhisms are not associated with susceptibility to chronic periodontitis in Turkish patients.
- Years 2 to 3 of life were a critical period: the participants whose families owned homes during these childhood years showed higher GR mRNA and lower TLR4 mRNA during adolescence, a profile that suggests better regulation of inflammatory responses
- TLR4 gene polymorphisms are not significantly associated with the susceptibility to, or severity of, chronic periodontitis in a Czech population.
- Polymorphisms of innate immunity receptors, especially TLR4 mutation, were associated with higher risk of cytomegalovirus infection.
- Lipopolysaccharide can induce human T cells to adhere to fibronectin via TLR4 signaling.
- Evidence is presented that 299glycine and 399isoleucine alleles of TLR4 result in weak innate immune responses in both transfected bronchial epithelial cells and monocytes from children with these alleles, following exposure to bacterial or viral stimuli
- Finds that Asp299Gly TLR-4 receptor polymorphism is not associated to a significant degree with aortic arteriosclerosis
- Syncytiotrophoblastss expressed TLR-2 & TLR-4, but myofibroblasts expressed only TLR-4; results indicate that there exist cell type-specific patterns of TLR function in placenta which likely regulate innate immune response at the maternal-fetal interface
- The PRBC group had a significantly different expression profile included up-regulation of the toll-like receptor 4. PRBCs activate inflammatory genes in circulating leukocytes.
- Altered TLR4 and adaptor protein expression might impair TLR4 signaling and explain the weak mucosal response to urinary tract infection in patients who develop asymmetric bacteriuria rather than symptomatic disease.
- Potential role for activation through TLR-4 in the inflammation and joint destruction of rheumaatoid arthritis.
- In unstable angina patients oxidized LDL may contribute to upregulating TLR-4 expression in monocytes.
- Transcription factor PU.1 controls transcription start site positioning and alternative TLR4 promoter usage.
- Fibrinogen alone and fibrinogen plus C5a are potent inducers of IL-8 production in monocytes, and signaling by fibrinogen is mediated through the TLR-4 pathway.
- E. coli modulates S100A15 and IL-8 expression of keratinocytes by recognition through TLR4.
- TLR2, TLR4, and NOD2 are involved in the recognition of M. paratuberculosis by the innate immune system.
- The decreased let-7 expression is associated with C. parvum-induced up-regulation of TLR4 in infected cells.
- P. gingivalis, therefore, selectively up-regulated CCR5 by two independent signaling pathways, Rgp acting on PAR-1 and PAR-2, and LPS on TLR2 and TLR4.
- Suppression of TLR4 signaling pathway may be an effective treatment for atherosclerosis.
- First study to show a role for Toll-like receptor 4 in the antibody response to whole-cell pertussis vaccination in 1-year-old children.
- NF-kappaB recruits E2F1 to fully activate the transcription of NF-kappaB target genes.
- Study found that among pleural fluid lymphocytes, natural killer cells are a major source of early IFN-gamma upon M. tuberculosis stimulation and Toll-like receptor 2 and 4 agonists activate NK cells but do not induce IFN-gamma like M. tuberculosis does.
- Two TLR4 polymorphisms heterozygosity is highly associated with symptomatic RSV disease in high-risk infants and supports a dual role for TLR4 SNPs in prematurity and increased susceptibility to RSV not revealed by analysis of either alone.
- TLR4 polymorphisms were not associated with primary outcome of liver transplantation for chronic hepatitis C virus.
- examined the suppression mechanism of lipopolysaccharide (LPS)-induced, namely Toll-like receptor 4 (TLR4)-mediated, activation of NF-kappaB and AP-1 in measles virus-infected monocytic cells
- Ciprofloxacin inhibits lipopolysaccharide-induced toll-like receptor-4 and 8 expression on human monocytes derived from adult and cord blood.
- Mrp8 specifically interacts with the TLR4-MD2 complex, thus representing an endogenous ligand of TLR4.
- Based on structural analysis and mutagenesis experiments on MD-2 and TLR4, we propose a model of TLR4-MD-2 dimerization induced by LPS.
- TLR4 is hyperexpressed in the intestinal mast cells of Crohn disease patients.
- TLR-4 gene polymorphisms are associated with lower levels of P-selectin and von Willebrand factor among hypercholesterolemic patients.
- TLR4 Asp299Gly is associated with inflammatory bowel diseases in whites.
- Patients with severe and mild malaria showed increased surface expression of TLR2 and TLR4 on CD14(+)monocytes and myeloid dendritic cells and decreased intracellular expression of TLR9 on plasmacytoid dendritic cells compared to healthy controls.
- Induced TLR2 cooperated with TLR4 to amplify iNOS induction in gastric mucosa infected with Helicobacter pylori which contain lipopolysaccharide as a pathogen.
- No correlation was demonstrated between TLR4 polymorphisms and susceptibility to Q fever.
- Expressions of both TLR2 and TLR4 at the vessel wall synergistically accelerated atherosclerosis. The present study revealed the role of TLRs expressed locally at the vessel wall in the early stage of atherosclerosis
- demonstrate a critical role for TLR4 in the development of necrotizing enterocolitis through effects on enterocyte injury and repair, identify a novel TLR4-focal adhesion kinase association in regulating enterocyte migration
- In human neutrophils, Helicobacter pylori induces an early inflammatory response, partially mediated via TLR2 and TLR4 activation.
- We hypothesized that polymorphisms in inflammatory response genes contribute to the increased susceptibility to acute otitis media in otitis-prone children.In the patient group, the TLR4 299 A/A genotype was associated with an otitis-prone condition
- a novel link between TLR4 and a calcium-dependent signaling cascade comprising CaMKIV-CREB-Bcl-2 that is essential for DC survival.
- TLR4 variants were not major risk factors for Crohn's disease in New Zealand population, but may associations with disease worldwide.
- Host-derived factors (IFN-gamma and TLR4 ligand) and viral factors (TLR2 ligand) act in tandem to induce and maintain monocyte/macrophage activation, thus favoring persistent inflammation in patients with cHCV infection.
- Fcgamma receptor IIA is involved in the neutralization of lipopolysaccharide signaling via a potent novel anti-TLR4 monoclonal antibody 15C1
- Two polymorphisms of TLR4, Asp299Gly and Thr399Ile, have unique distributions in populations from Africa, Asia, and Europe.
- Toll-like receptor 4 (TLR4) gene polymorphisms in celiac disease were studied.
- M-Ficolin expression is silenced in macrophages but can be re-activated after prolonged activation via TLR2 and TLR4
- Transfer of endotoxin from MD-2 to extracellular soluble CD14 reduces activation of cells expressing TLR4 without MD-2.
- Suggest that TLR2/4 may play role in aortic valve inflammation and stenosis.
- Nerve growth factor facilitates TLR4 signaling-induced maturation of human dendritic cells through LPS-up-regulated p75(NTR) via activation of p38 MAPK and NF-kappaB pathways
- frequency of the C/C genotype at base-pair position +3725 was significantly higher in both the moderate and the severe periodontitis patient group than in the control group
- TLR4/MD-2 complex is responsible for recognition of Rhodococcus spheroides lipopolysaccharide as an agonist in human cells.
- TLR4 expression on mesenchymal stem cells (MSCs) may provide an effective mechanism to block the immunosuppressive activity of MSCs and therefore to restore an efficient T-cell response in the course of dangerous infections
- TLR4 does not play a major role in the predisposition to suffer from multiple sclerosis in Spain population.
- These findings strongly suggest that the structural properties of (endotoxin) E.MD-2, not E alone, determine agonist or antagonist effects on TLR4.
- These observations provide the first evidence for a role of the key innate immune receptor, TLR4, in neuroinflammation in Alzheimer's disease.
- TLR4 directly protected the oral mucosa from fungal infection via a process mediated by polymorphonuclear leukocytes (PMNs).
- Toll-like receptor 4 gene expression was increased after stimulation with native low-density lipoprotein (nLDL) and oxidized LDL.
- The G allele of the TLR-4 gene Asp299Gly polymorphism is associated with increased carotid artery compliance in young adults
- No significan correlation between TLR4 single nucleotide polymorphism and thrombosis risk in myeoloproliferative disorders.
- HIV-2 gp105 activates TLR4 signaling and induces TNF-alpha production by monocytes.
- Mechanisms regulating IL-6 production led to the discovery that the Tec kinase bone marrow tyrosine kinase gene in chromosome X (Bmx) regulates Toll-like receptor 4-induced IL-6 production.
- TLR4 expression and signaling are increased in type 1 diabetes mellitus and contribute to the proinflammatory state.
- results suggest that hyaluronan fragments in melanoma might promote tumor invasiveness by inducing MMP- and cytokine-expression, in part in a TLR4-dependent manner, providing new insights into the relationship between cancer and innate immunity
- TLR4 expression in respiratory epithelium is altered in chronic obstructive pulmonary disease. Expression is modulated by drugs used to treat airways inflammation and by cigarette smoke.
- Dysregulation of TLR2, TLR4, and CD14 expression in different parts of the intestinal mucosa may be crucial in IBD pathogenesis.
- Exclusive TLR4 expression may enable gastric extranodal marginal zone B-cell lymphomas of MALT type to interact with H. pylori and autoantigens.
- These findings suggest that the vascular smooth muscle cells of atherosclerotic coronary arteries may be activated to express TLR4
- CF airway PMNs expressed enhanced level of TLR4.
- Role of TLR4 polymorphisms in inflammatory responses: implications for unsuccessful aging.
- The present study failed to find any significant association between polymorphisms and generalized aggressive periodontitis
- M. bovis BCG, acting through both TLR2 and TLR4, induces the activation of the ERK1/2 MAPK pathway, which in turn plays a major role in CXCL8 secretion.
- tyrosine phosphorylation of Mal is required for adapter signaling, regulates Mal interactions with TLR4 and receptor signaling, and is inhibited in endotoxin tolerance
- TLR-4 Thr399Ileu substitution may be a risk factor for gastritis and precancerous lesions.
- IRF-1 silencing through RNA interference, leads to an overexpression of TLR-4 in THP-1 cells.
- Estimation of TLR2 expression on antigen presenting cells may be predictive of in acute rejection after liver transplantation.
- Benign prostate epithelial cells express both TLR 4 (LPS-specific) and TLR 9 (CpG-specific) when exposured to lipopolysaccharide (LPS) and CpG DNA.
- No evidence was found of an association between TLR4, CCR2, and CCL2 and AMD (age-related macular degeneration)
- inflammatory bowel disease not associated with the TLR4 c.896A>G (p.D299G) variant
- Combination of lipid A hypoacylation and TLR4 single nucleotide polymorphisms would exhibit a compounded effect on TLR4 signaling.
- The Mal S180L and TLR4 G299D polymorphisms do not contribute to RA susceptibility or severity either individually or in combination.
- Murine beta-defensin 2 (mDF2beta) can act as an endogenous ligand for TLR-4-activating maturation of dendritic cells.
- The functional association between TLR4 and the S1P1 receptor demonstrates a novel mechanism in the regulation of IFN-beta and CXCL-10 in human primary gingival epithelial cells.
- present study investigated cellular factors involved in TLR-4-mediated IL-6 in VSMC in terms of MAPK and transcription elements
- TLR 4 A299G appears to be a significant risk factor for CD, in particular colonic, nonstricturing disease.
- Upregulated TLR4 is associated with HO-1 reduction in peripheral blood monocytes from patients with Behcet's disease, leading to augmented inflammatory responses.
- Suggest that syntenin is a physiological suppressor of TRAF6 and plays an inhibitory role in IL-1R- and TLR4- mediated NF-kappaB activation pathways.
- TLR4 expression in human antral and corpus gastric mucosa is significantly increased during H. pylori infection
- Toll-like receptor 4 mediates induction of the Bcl10-NFkappaB-interleukin-8 inflammatory pathway by carrageenan
- TLR4 signaling is not deficient in hyper-IgE patients.
- A significant association was observed between allele G on Asp299Gly (Toll Like Receptor4) and chronic cavitary pulmonary aspergillosis
- Results show that the distributions of the 119C>A genotype of the TLR4 gene were similar in patients with mild or severe acute pancreatitis.
- TLR1, 2, and 4 protein colocalized with adiponectin in human adipocytes.
- TLR4 expression is differentially modulated on the different subsets of T cells depending on their activation status and cytokine expression.
- TLR4 coordinates the activation of two distinct signaling pathways (TIRAP-MyD88 and TRAM-TRIF adaptor proteins) from an intracellular location in a process organized around endocytosis of the TLR4 complex.
- Minor alleles of several TLR4 variants, although not directly associated with type 2 diabetes might increase the risk for type 2 diabetes in subjects with high TC/HDL-C
- TAK-242 is a selective inhibitor of signaling from the intracellular domain of TLR4 and represents a novel therapeutic approach to the treatment of TLR4-mediated diseases.
- Review provides tremendous insights the lipopolysaccharide/TLR4 signaling pathway, which induces the release of critical proinflammatory cytokines that are necessary to activate potent immune responses.
- racial difference can be found in the frequency of the TLR4 polymorphism
- Prior knockdown of TLR4 blocked both lipopolysaccharide-induced SRC family PTK activation and barrier disruption
- Results indicate that lipopolysaccharide-induced activation of Toll-like receptor 4 in chorioamnionitis triggers increased production of beta-defensin 3.
- the low frequency of TLR2 and TLR4 polymorphisms observed here and in other populations corroborates and suggests that these do not play an important role in Chagas' disease.
- TLR4 variant clearly reduces its potency to mediate signaling.
- TLR4 and NOD2 gene variants are associated with a pro-inflammatory phenotype with a history of early-onset preeclampsia and HELLP syndrome
- TLR variants are unlikely to have a major impact on overall AMD risk, and the common variants studied were not associated with AMD.
- TLR4 and G protein-coupled receptors can interact to enhance cytokine production in epithelial cells
- Specific inhibition of LPCAT down-regulated inflammatory cytokine production in monocytes and epithelial cells by preventing translocation of TLR4 into membrane lipid raft domains.
- one SNP in TLR4 is associated with Behcet's disease, and six SNPs have an effect on clinical features of Behcet's disease
- cells that express TLR4 without MD-2 and whose response to LPS depends on ectopically produced MD-2 were most affected by expression of the G56R variant of MD-2.
- Vasoactive intestinal peptide acts as a negative modulator of the TLR4-signaling by overturning the production of several checkpoints molecules of the cascade and thus, widening its potential therapeutic effects.
- scaffold protein MyD88 as the link coupling TLR2,4 to PKCepsilon recruitment, phosphorylation, and downstream signaling.
- HIF-1alpha protein is selectively required for down-regulation of ASK1 activated during lipopolysaccharide-induced TLR4 downstream signalling.
- monocyte activation in hepatitis C patients leads to deficient TLR4 signaling in these cells
- The study reports an association between TLR4 polymorphisms (299 and/or 399) and atopic hypersensitivity-related phenotypes in a nonsmoking population.
- the monomeric form of sMD-2 is the active species both for reaction with endotoxin.CD14 and Toll-like receptor 4 (TLR4), as needed for potent endotoxin-induced TLR4 activation
- TLR-4 signaling in small intestinal epithelium promotes B-cell recruitment and IgA production in lamina propria.
- TLR4 may participate in cerebral ischemic injury through an MyD88-independent signal pathway.
- microfilariae interfere with monocyte-derived DC function by altering TLR3 and TLR4 expression and interfering with both MyD88-dependent signaling and a pathway that ultimately diminishes NF-kappaB activity
- TLR4 may play a key role in the pathogenesis of myasthenia gravis. It was the thymic tissues adjacent to thymomas but not thymomas themselves participated in the onset of MG.
- Interaction between TLR4 expression and the pathogenesis of chronic hepatitis B.
- dectin-1 synergizes with both TLR2 and TLR4 pathways for the production of TNF-alpha in human primary PBMCs and in monocyte-derived macrophages.
- The minor allele of the TLR4 SNP, rs1927911, was associated with a lower risk of MI (odds ratio 0.88, 95% confidence interval 0.77 to 0.99).
- Oxidized phospholipid inhibition of toll-like receptor (TLR) signaling is restricted to TLR2 and TLR4: roles for CD14, LPS-binding protein, and MD2 as targets for specificity of inhibition.
- expression of TLR1, TLR2, TLR4 and TLR6 transcripts was significantly lower in peripheral blood mononuclear cells from chronic hepatitis B virus-infected patients
- Multiple SNPs in the TLR4 gene are associated with the risk of NTG (normal tension glaucoma).
- Human heat-shock protein 70 is involved in TLR4-mediated growth of endometrial cells derived from women with endometriosis.
- Activation of TLR4 signaling in bladder cancer cells up-regulated B7-H1 expression. This regulation was significantly attenuated by ERK or JNK inhibitor.
- [prevalence of] Asp299Gly and Thr399Ile polymorphisms seemed to be rather low in the Chinese population, which did not permit any conclusion regarding its effects on periodontitis
- Analysis of proteinase-activated receptor 2 and TLR4 signal transduction: a novel paradigm for receptor cooperativity.
- Data support a link between TLR4 expression and long-term graft outcome. Absence of TLR signaling may be a feature of tolerance and increased TLR4 signaling may be implicated in chronic rejection.
- TLR4 (toll-like receptor 4) polymorphisms showed an association with Ankylosing Spondylitis in the Finns only, not patients from the United Kingdom
- defensin beta 2 production is mediated by TLR2 and TLR4 activation and involves a c-Fos-mediated, protein kinase C-dependent signaling pathway
- TLR4 expressed on human PC3 cells is functionally active, and may play important roles in promoting prostate cancer immune escape, survival, progression, and metastasis by inducing immunosuppressive and proangiogenic cytokines.
- The species-specific difference between human and murine MD-2 activation of TLR4 by PTX can be explained by alterations of surface charge distribution (i.e. electrostatic potential), binding pocket size, and the locus of PTX binding within the MD-2 pocke
- These findings indicated that the polymorphisms of CD14, but not TLR4 Asp299Gly and Thr399Ile mutations, may be an important genetic factor for HBV-related cirrhotic injury in the Chinese Han population.
- In inflammatory bowel disease patients selected from Southern Italy, the NOD2/CARD15, but not TLR4 single nucleotide polymorphisms, are associated with increased risk of Crohn's disease.
- TLR2 and TLR4 was significantly upregulated by Burkholderia cenocepacia infection in lung epithelial cells.
- fibrinogen activates TLR4, explaining how fibrinogen promotes inflammatory protein expression
- TLR4 variations and statins have an additive inhibitory effect on TLR4-mediated inflammatory response
- No association between TLR4 Asp299Gly and Thr399Ile gene polymorphisms and preeclampsia is indicated.
- We found no evidence that the gene polymorphism of TLR4 (p = 1.000) and overall gene polymorphism in any of the genes (p = 0.752) correlate with periodontitis.
- caspase-8 has a role in the production of biologically active IL-1beta in response to TLR3 and TLR4 stimulation
- no difference was found in the genotype and allele frequencies of TLR4 between patients with type 1 diabetes mellitus (T1DM), celiac disease (CD), both T1DM and CD and controls
- Estradiol regulates MICA expression in human endometrial cells.
- H pyloriSS1-lipopolysaccharides induces IL-8 production through activating TLR4 signaling in SGC-7901 cells
- Toll-like receptor signaling 4 may induce placental corticotropin-releasing hormone expression through myeloid differentiation primary response gene (MyD88).
- Our data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.
- pneumolysin selectively induced expression of MKP1 via a TLR4-dependent MyD88-TRAF6-ERK pathway, which inhibited the PAK4-JNK signaling pathway,leading to up-regulation of MUC5AC mucin production
- HP0175 transactivates epidermal growth factor receptor through TLR4 in gastric epithelial cells
- PI3K activation (by HIV proteins such as Nef) may contribute to reduced TLR4-mediated TNF-alpha release in HIV+ human macrophages and impair host cell response to infectious challenge.
- stearoyl-arachidonoyl form of phosphatidylserine disrupted the association of both TLR4 and TLR2 with their respective membrane partners that are required for signaling
- Workers with TLR4 variants that reduce responsiveness to endotoxin have higher risks for laboratory animal and other allergen sensitization but spend longer hours in tasks with high endotoxin and animal allergen exposures.
- These results support a model in which sMD2 binds to TLR4 and increases TLR4 levels at the cell surface by preventing TLR4 turnover through the endocytic pathway.
- FLN29, in addition to playing a negative regulatory role in the TLR4 signaling pathway, negatively regulates the RIG-I-like helicase signaling pathway at the level of IPS-1/TRAF6 and IPS-1/TRAF3 complexes
- Data demonstrate a significant relationship between maternal and fetal TLR4 genotype and chorionic plate inflammation. This maternal and fetal genotypic effect are independent of each other as well as other environmental covariates.
- Chemokine induction in dendritic cells by CbpA and Ply may be important for their potential use in future pneumococcal vaccines.
- This study suggests an association between the donor TLR4 haplotype S4 and the risk of invasive aspergillosis among recipients of hematopoietic-cell transplants from unrelated donors.
- study provides evidence that IL-10 release requires stronger triggering of TLR4 than TNF release; lower number of responsive TLR4 receptors on monocytes of heterozygous carriers of Asp(299)Gly polymorphism may explain why only IL-10 release is affected
- results reject the hypothesis that functionally relevant mutations have a major effect on aggressive periodontitis susceptibility
- Significant & strong 2- & 3-locus interactions between SNPs in TOLLIP (rs4963060), TLR4 (rs6478317) & IRAK1 (rs1059703)were associated with the response to whole-cell vaccine pertussis vaccination in 490 1-yr-old children.
- HIV-1-infected individuals carrying a mutant TLR4 allele appear more likely to have multicentric Castleman's disease, a lymphoproliferation associated with enhanced KSHV replication.
- Toll-like receptors 4 highly expressed on human melanoma cells.
- Our results demonstrate that the +896A/G TLR4 single nucleotide polymorphism (SNP) is associated with Alzheimer disease
- This study explored whether Klebsiella pneumoniae upregulates the expression of TLRs in human airway epithelial cells.
- SOCS1-regulation of the IFN beta-dependent component of the LPS-induced TLR4 signaling pathway may contribute to the down-regulation of inflammatory cytokine production
- Toll-like receptor 2, 4, and 9 overexpression is associated with neutrophil dysfunction in alcoholic hepatitis.
- Autoantibodies that bind to the surface of fibroblasts may contribute to the pathogenesis of systemic sclerosis by up-regulating the fibroblast production of profibrotic and proangiogenic chemokines, in a proteasome- and TLR-4-dependent manner
- high expression of TLRs 3 and 4, at an early stage of rheumatoid arthritis and the reactivity of synovial fibroblasts in vitro suggest that TLR signaling pathways resulting in inflammation and joint destruction are activated early in the disease process
- There was no intraction between TLR4 allele carrier status and H.pylori antibodies on serum total IgE .
- Genetic polymorphisms in TLR4, genes are not associated with malaria resistance in patients from Baixo Amazonas region, Brazil
- Characteristic patterns in the expression of TLR2 and TLR4 on monocytes and granulocytes were found in venous blood of patients undergoing cardiac surgery with or without cardiopulmonary bypass.
- TLR4 expression was up-regulated in non-cancerous tissues or down-regulated in cancerous tissues in patients with colorectal cancer
- TLR4 is functional and expressed in the developing intestinal mucosa; TLR4 signaling in enterocytes plays a critical role in the pathogenesis of necrotizing enterocolitis.
- Multi-hit inhibition of circulating and cell-associated components of the toll-like receptor 4 pathway by oxidized phospholipids.
- TLR4 activation by lipopolysaccharide is able to induce robust interferon (IFN)-alpha production by human monocytes that have been pretreated with type I IFN.
- TLR4 htSNPs are associated with risk of developing complicated sepsis.
- TLR4 polymorphisms were associated with the presence of coronary stenosis.
- Toll-like receptors 4 and 5 induce distinct types of vasculitis.
- Data show that there were non-association and non-additional effects of TLR4/CD40 gene polymorphisms and haplotypes upon asthma risk.
- Toll-like receptor 4 has a role in protection from lethal gram-negative bacterial sepsis
- No polymorphisms in the NOD2 and TLR4 genes were found to be associated with the development of gastric MALT lymphoma.
- TLR4+3725 G/C polymorphism was a risk factor of gastric atrophy in H. pylori seropositive Japanese.
- Greater expression of TLR2 and TLR4 and greater pro-inflammatory and pro-osteogenic responses to TLR4 agonists in AVICs than PVICs are associated with osteogenic phenotypic changes
- lactate boosts TLR4 activation and NF-kappaB-dependent inflammatory gene expression via monocarboxylate transporters and MD-2 up-regulation.
- TLR4-mediated activation of HIV-LTR is largely governed by the nuclear factor-kappaB pathway.
