TAK-242 (resatorvid), a small molecule specific inhibitor of Toll-like receptor (TLR) 4 signaling, inhibits the production of lipopolysaccharide-induced inflammatory mediators by binding to the intracellular domain of TLR4. Previously, Cys747 in TLR4 was identified as the binding site of TAK-242. However, the mechanism by which TAK-242 inhibits TLR4 signaling after binding to TLR4 remains unknown. The present study demonstrated, using coimmunoprecipitation, that TAK-242 interferes with protein-protein interactions between TLR4 and its adaptor molecules. Among ten different human TLRs, TAK-242 selectively bound to TLR4. The time course of the inhibitory effect of TAK-242 on inflammatory mediator production corresponded to that of the binding of TAK-242 to TLR4. TAK-242 inhibited the association of TLR4 with TIR domain-containing adaptor protein (TIRAP) or TRIF-related adaptor molecule (TRAM) in HEK293 cells overexpressing TLR4, MD-2 and TIRAP or TRAM, respectively. TAK-242 inhibited the ...http://molpharm.aspetjournals.org/content/early/2010/09/29/mol.110.068064
A role for the adaptor proteins TRAM and TRIF in toll-like receptor 2 signaling
Toll-like receptors (TLRs) are involved in sensing invading microbes by host innate immunity. TLR2 recognizes bacterial lipoproteins/lipopeptides, and lipopolysaccharide activates TLR4. TLR2 and TLR4 signal via the Toll/interleukin-1 receptor adaptors MyD88 and MAL, leading to NF-κB activation. TLR4 also utilizes the adaptors TRAM and TRIF, resulting in activation of interferon regulatory factor (IRF) 3. Here, we report a new role for TRAM and TRIF in TLR2 regulation and signaling. Interestingly, we observed that TLR2-mediated induction of the chemokine Ccl5 was impaired in TRAM or TRIF deficient macrophages. Inhibition of endocytosis reduced Ccl5 release, and the data also suggested that TRAM and TLR2 co-localize in early endosomes, supporting the hypothesis that signaling may occur from an intracellular compartment. Ccl5 release following lipoprotein challenge additionally involved the kinase Tbk-1 and Irf3, as well as MyD88 and Irf1. Induction of ...https://brage.bibsys.no/xmlui/handle/11250/2458403
Toll - Like Receptor 2 Agonists - Pipeline Insights, 2017 | Healthcare
Before It's News). Publisher's, "Toll-Like Receptor 2 (TLR-2) Agonists-Pipeline Insights, 2017″, report provides in depth insights on the pipeline drugs and their development activities around the Toll-Like Receptor 2 (TLR-2) Agonists. The Publisher's Report covers the product profiles in various stages of development including Discovery, Pre-clinical, IND, Phase I, Phase II, Phase III and Preregistration. Report covers the product clinical trials information and other development activities including technology, licensing, collaborations, acquisitions, fundings, patent and USFDA & EMA designations details. Publisher's Report also provides detailed information on the discontinued and dormant drugs that have gone inactive over the years for Toll-Like Receptor 2 (TLR-2) Agonists. Publisher's Report also assesses the Toll-Like Receptor 2 (TLR-2) Agonists therapeutics by Monotherapy, Combination products, Molecule type and Route of ...http://beforeitsnews.com/healthcare/2017/02/toll-like-receptor-2-agonists-pipeline-insights-2017-2502956.html
Association of Toll-Like Receptor 4 Asp299Gly and Thr399Ile Polymorphisms with Increased Infection Risk in Patients with...
Background. The Toll-like receptor 4 (TLR4) is an essential component of the innate immune response to various microorganisms. We investigated the association between TLR4 polymorphism and the risk of acquiring severe infections, in patients with human immunodeficiency virus (HIV)-1 infection.. Methods. The presence of TLR4 Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs) was determined in a cohort of 199 HIV-1 infected patients and evaluated in relation to the occurrence of various infections.. Results. One hundred seventy-two patients were homozygous for the wild-type genotype; 22 patients (11%) were heterozygous for both SNPs; 4 were heterozygous for 1 polymorphism; 1 patient was heterozygous for the Asp299Gly SNP and homozygous for the Thr399Ile SNP. Of individuals with a nadir CD4 cell count of ,100 cells/mm3, those who carried both SNPs, compared with those who carried the wild-type genotype, demonstrated a ,3-fold increase in the odds ratio (OR) of any serious infection ...http://oxfordindex.oup.com/view/10.1086/653607
Developing polymer-drug complex based toll-like receptor (TLR-2/TLR-4) antagonist for modulating gut innate immune system to...
Continuous inflammation in the colon often leads to chronic diseases such as inflammatory bowel disease (IBD) and colorectal cancer. Recent evidence strongly suggests the role of Toll-Like Receptors 2 and 4 in the etiology of aforementioned diseases. Therefore, pharmacological inhibition of TLR-2/TLR-4 has been a new promising strategy for preventing inflammation in IBD and colorectal cancer. In the current study, we have developed a novel polymer-drug complex (Ora-Curcumin) as a TLR-2/TLR-4 antagonist to modulate the gut innate immune system. Ora-Curcumin is a molecular complex of curcumin with a hydrophilic polymer Eudrgit® S100 prepared by nano-precipitation. Ora-curcumin is more water soluble (~1000 times) and stable than curcumin in aqueous buffers. It is water soluble only at pHs above 6.8. Therefore, once consumed orally, it is expected to be soluble and functionally available only at the luminal side of the colon where the pH reaches 6.8. In addition, Ora-Curcumin ...http://www.jimmunol.org/content/198/1_Supplement/81.20
"Toll-like Receptor 4 (TLR4) in Acute and Chronic Renal Diseases" by Anand R. Nair
Despite advances in its treatment, the incidence of renal diseases has been consistently increasing. Hence, there is a need to understand the underlying molecular mechanisms of the progression of kidney diseases. Recent research implicates inflammation as an important mediator of renal injury. We hypothesized that inhibiting Toll-like receptor 4 (TLR4), an upstream modulator of several inflammatory pathways, would prevent the progression of renal diseases. First, we determined the mechanism by which AngiotensinII (AngII)-induced inflammation is modulated by TLR4 using an in vitro model of rat tubulo-epithelial cells. We blocked TLR4 using gene silencing strategy in NRK52E cells. In TLR4-silenced cells, the expression of TLR4 was decreased, activation of NF-κB was reduced, inflammation and oxidative stress were attenuated, suggesting a role for TLR4 in potentiating AngII-induced renal inflammation. We then focused on an in vivo acute kidney injury (AKI) model to elucidate the effect of TLR4 ...https://digitalcommons.lsu.edu/gradschool_dissertations/3632/
anti-Tlr3 antibody | Rabbit Toll-like Receptor 3 (TLR3) Polyclonal Antibody-NP 942086.1
Buy anti-Tlr3 antibody, Rabbit Toll-like Receptor 3 (TLR3) Polyclonal Antibody-NP_942086.1 (MBS194448) product datasheet at MyBioSource, Primary Antibodies. Application: Western Blot, Immunohistochemistryhttps://www.mybiosource.com/prods/Antibody/Polyclonal/Toll-like-Receptor-3-TLR3/Tlr3/datasheet.php?products_id=194448
eCite - C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in...
C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diethttp://ecite.utas.edu.au/80245
Differential Expression and Regulation of Toll-Like Receptors (TLR) in Human Leukocytes: Selective Expression of TLR3 in...
Despite the assumption that at least some TLR family members mediate innate immune response, very little information was available regarding their expression pattern in immunocompetent cells and no functional data are available for TLR other then TLR2 and TLR4. The existence of many of them may reflect specialized functions, redundancy, and/or differential expression and roles in different cell types. Herein, we have characterized the pattern of mRNA expression of the first five TLR.. We separated fresh human monocytes, NK cells, PMN, B cells, T lymphocytes, Th1 or Th2 lymphocytes, and monocyte-derived DC. Total RNA was extracted from the cells and analyzed by Northern blot to detect specific TLR transcripts. To note, TLR1, TLR2, and TLR4 probes allowed a signal detection on the filter only after a few hours of autoradiography. On the other hand, TLR3 and TLR5 probes required at least an overnight exposure of the filter to evidence a specific transcript, suggesting that distinct TLR transcripts ...http://www.jimmunol.org/content/164/11/5998.long
Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. - The...
Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury, or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4)-mediated sterile inflammation. Here we map three sites within tenascin-C that directly and cooperatively interact with TLR4. We also identify a conserved inflammatory epitope in related proteins from diverse families, and demonstrate that its presence targets molecules for TLR detection, while its absence enables escape of innate immune surveillance. These data reveal a unique molecular code that defines endogenous proteins as inflammatory stimuli by marking them for recognition by TLRs.https://www.kennedy.ox.ac.uk/publications/730422
TLR3, Toll-like receptor 3, or CD283 Antibody
Research proven purified goat polyclonal TLR-3 (Toll-like receptor3)/CD283 antibody. Designed for immune response research. Excellent for western blotting, DIRECT Elisa and related applications.https://www.neuromics.com/MO15121
Abstract 3601: Toll-Like Receptor-2/-6 Stimulation Promotes Angiogenesis and Reendothelialization | Circulation
Introduction: Toll-like receptors (TLRs) are crucial for the recognition of pathogens which subsequently lead to the activation of inflammatory pathways. However, the mycoplasma lipopeptid and TLR-2/-6 ligand MALP-2 has been used in therapeutic applications, e.g. dermal wound healing. Since tissue regeneration requires the reestablishment of a functional vascular network we investigated the impact of the TLR-2/6 ligand MALP-2 on angiogenesis and reendothelialization.. Methods and results: Expression of TLR-2 and -6 in human endothelial cells was demonstrated by PCR, Western blot and immunofluorescence and significantly up regulated after stimulation with MALP-2 (100 ng/mL, qRT-PCR, Western blot). MALP-2 induced tube formation (Matrigel, P,0.05) and endothelial cell proliferation (BrdU-incorporation, P,0.01) in vitro which could be inhibited with neutralizing antibodies against TLR-2/-6. Furthermore, MALP-2 enhanced neovascularisation of matrigel implants in mice as ...http://circ.ahajournals.org/content/118/Suppl_18/S_449.2
Cutting Edge: Repurification of Lipopolysaccharide Eliminates Signaling Through Both Human and Murine Toll-Like Receptor 2 |...
The role of TLR2 in LPS signaling has been very controversial. Certainly, the original reports of TLR2-mediated signaling in transfected 293 cells were quite convincing (10, 11), and similar results have been reported by numerous laboratories (14, 16, 18, 20, 22, 25, 39). However, once it was demonstrated that TLR2-deficient mice responded normally to LPS, while TLR4-deficient mice were refractory (7, 8, 9, 13), the physiological role of TLR2 in LPS signaling came under more careful scrutiny. Several groups, in fact, have demonstrated LPS signaling in the absence of TLR2 in various primary cells and cell lines (14, 15, 20, 21, 24, 25, 40). The data presented in this report attempt to clarify the putative contribution of TLR2 to LPS signaling.. Our results suggest that the overexpression of either human or murine TLR2 causes cell lines to become extremely sensitive to the potent "endotoxin protein" contaminants present in many commercial LPS preparations. Our data clearly point to non-LPS ligands ...http://www.jimmunol.org/content/165/2/618
Molecules and Cells
In patients with HBV infection, antiviral therapy is a long-term and effective treatment. Unfortunately, many patients with CHB have a drug-resistant disease, and antiviral treatment is ineffective in these patients after a long duration of therapy. Thus, the identification of a baseline factor that predicts the outcome of antiviral treatment is urgently needed. IP-10 and its non-cognate receptor Toll-like receptor 4 (TLR4) are involved in the pro-apoptotic signalling cascade during liver injury; thus, antagonism of the chemokine C-X-C motif ligand (CXCL) 10/TLR4 pathway may be a therapeutic option for patients with liver diseases associated with increased apoptosis (Sahin et al., 2013). Although the use of IP-10 as a prognostic marker to predict the outcomes of antiviral therapy still faces significant opposition, lower serum IP-10 levels at year 0 were the only factor associated with HBsAg seroclearance in a previous study (Wong et al., 2016). Moreover, baseline IP-10 levels were ...http://molcells.inforang.com/journal/view.html?doi=10.14348/molcells.2017.0051&sort=&scale=12&key=&keyword=&s_v=&s_n=&pn=&year=&page=
Ation was dependent on TLR7. Hence, while TLR8 is expressed on | GlyT1 inhibitor glyt1inhibitor.com
Ation was dependent on TLR7. Thus, despite the fact that TLR8 is expressed on MedChemExpress Crenolanib murine microglia and astrocytes, it appears to onlyhttp://glyt1inhibitor.com/index.php/2017/08/18/ation-was-dependent-on-tlr7-hence-while-tlr8-is-expressed-on/
Cutting Edge: A Common Polymorphism Impairs Cell Surface Trafficking and Functional Responses of TLR1 but Protects against...
Fluorescence microscopy revealed a punctuated pattern of TLR1 staining on monocytes derived from individuals who express surface TLR1 (Fig. 1⇑B, top left panel). Conversely, monocytes derived from donors who did not express surface TLR1 exhibited no detectable signal above that observed with an isotype control Ab (Fig. 1⇑B, top right panel). When cells were permeabilized before staining, intracellular TLR1 was detected in both groups in a diffuse pattern (Fig. 1⇑B, bottom panels). However, monocytes that lacked cell surface TLR1 exhibited a greater intensity of intracellular staining that was distributed predominantly within the perinuclear region of the cell (Fig. 1⇑B, bottom right panel). These results show that an inability to transport TLR1 to the cell surface underlies the deficiency in surface expression and suggests that instead the receptor accumulates within the cell, possibly within the endoplasmic reticulum or Golgi network.. Since no defect in surface expression of the ...http://www.jimmunol.org/content/178/12/7520.long
Monocytes Heterozygous for the Asp299Gly and Thr399Ile Mutations in the Toll-like Receptor 4 Gene Show No Deficit in...
It was expected that the responses of wild-type and heterozygote monocytes to S. aureus LTA should be broadly similar as the signaling of this molecule is thought to be TLR4 independent (11). This differential signaling could also explain the identical responses made toward P. gingivalis LPS as this molecule has been shown to be capable of signaling via TLR2 (2), though it should be pointed out that the LPS of at least one strain of P. gingivalis has been shown to signal via TLR4 (12). However, the responses of heterozygotes to every other LPS tested are at odds with recent reports of the reduced functional capacity of cells isolated from such donors. Arbour and coworkers have reported that individuals heterozygous for these mutations have blunted physiological responses to inhaled endotoxin and while airway epithelia from wild-type individuals are capable of secreting IL-1α in response to LPS in vitro, cells from heterozygotes were shown to be incapable of this response (5).. There are several ...http://jem.rupress.org/content/197/12/1787
DI-fusion Toll-like receptor (TLR)2 and TLR3 sensing is required for...
DI-fusion, le Dépôt institutionnel numérique de l'ULB, est l'outil de référencementde la production scientifique de l'ULB.L'interface de recherche DI-fusion permet de consulter les publications des chercheurs de l'ULB et les thèses qui y ont été défendues.http://difusion.ulb.ac.be/vufind/Record/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/53482/Details
Mechanical-stretch of C2C12 myoblasts inhibits expression of Toll-like receptor 3 (TLR3) and of autoantigens associated with...
Sigma-Aldrich offers abstracts and full-text articles by [Rong Chen, Liqiang Feng, Mo Ruan, Xinghui Liu, Sahil Adriouch, Hua Liao].https://www.sigmaaldrich.com/catalog/papers/24224022
OriGene - TLR10 (NM 030956) cDNA Clone
TLR10 - TLR10 (untagged)-Human toll-like receptor 10 (TLR10), transcript variant 1 available for purchase from OriGene - Your Gene Company.http://www.origene.com/human_cdna/NM_030956/SC125241.aspx
anti-TLR2 antibody | GeneTex
TLR2 antibody (toll-like receptor 2) for ELISA, IHC-P, WB. Anti-TLR2 pAb (GTX31279) is tested in Human, Mouse samples. 100% Ab-Assurance.http://www.genetex.com/TLR2-antibody-GTX31279.html
TLR6 - NBP1-54336 | acris-antibodies.com
TLR6, 50 µg. TLR6 is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity.https://www.acris-antibodies.com/antibodies/primary-antibodies/tlr6-nbp1-54336.htm
摘 要：Toll样受体4(TLR4)是固有免疫系统中能够识别病原相关分子模式的受体家族成员，可识别革兰氏阴性菌的脂多糖(LPS)而在细菌感染性疾病的发生中起重要作用。近年来越来越多的研究发现，TLR4还广泛参与病毒感染性疾病的发生和病毒的免疫逃逸，由于其信号转导通路的独特性和细胞定位的可变性，再次引起人们极大的研究兴趣。该文将介绍TLR4的生物学特性、信号转导通路及TLR4与病毒感染的最新研究进展 ...http://www.lifescience.net.cn/arts.asp?id=1222
DDX58 antibody | acris-antibodies.com
Antiviral inte immunity depends on the combition of parallel pathways triggered by virus detecting proteins in the Toll-like receptor (TLR) family and…https://www.acris-antibodies.com/target/ddx58-antibody.htm