Ask about this productRelated genes to: Sebi-1 TIRAP
- Gene:
- TIRAP NIH gene
- Name:
- TIR domain containing adaptor protein
- Previous symbol:
- -
- Synonyms:
- Mal, wyatt
- Chromosome:
- 11q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-06-05
- Date modifiied:
- 2016-06-17
Related products to: Sebi-1 TIRAP
*Please allow 3-5 days for delivery time.* In mammals, TIR domain adapters, including Myd88, TIRAP, TICAM-1 (also called TRIF), and TRAM, act in Toll-like receptor (TLR) signaling pathway. The last meAdaptor protein Wyatt,Homo sapiens,Human,MAL,MyD88 adapter-like protein,TIR domain-containing adapter protein,TIRAP,Toll_interleukin-1 receptor domain-containing adapter proteinAdaptor protein Wyatt,Mal,Mouse,Mus musculus,MyD88 adapter-like protein,TIR domain-containing adapter protein,Tirap,Toll_interleukin-1 receptor domain-containing adapter proteinAnti- TIRAP Mal (Isoform b) Antibodyanti-TIRAPanti-TIRAPanti-TIRAPanti-TIRAPanti-TIRAPanti-TIRAP (C-Terminus)anti-TIRAP (C-Terminus)Anti-TIRAP (human) (Sebi-1) Antibody (OAED00364)anti-TIRAP (N-Terminus)anti-TIRAP (N-Terminus)Anti-TIRAP Antibody Related articles to: Sebi-1 TIRAP
- Toll-like receptor 8 (TLR8) is crucial for detecting viral and bacterial ssRNA in mammals. However, its functional characteristics in early vertebrates remain largely unclear. Here, we employed the economically important fish Ctenopharyngodon idella, which harbors two TLR8 homologs (CiTLR8a/b), as a representative model. CiTLR8a/b are trafficked to early endosomes and lysosomes by UNC93B1, where they dynamically form homodimers and heterodimer, and bind ssRNA and dsRNA. Upon ligand binding, they first recruit MyD88, then TIRAP as adaptors. Unexpectedly, CiTLR8a enhances viral replication by suppressing downstream IFN, NF-κB, and AP-1 pathways in vitro and in vivo. In contrast, CiTLR8b is signaling-defective despite ligand binding and adaptor recruitment. Most strikingly, heterodimerization with signaling-inert CiTLR8b switches CiTLR8a into an antiviral sensor by remodeling intracellular TIR-domain conformation through extracellular LRR-ligand interaction. Further, structural and mutagenesis analyses identify critical functional determinants: specific residues (CiTLR8a-V116/S164; CiTLR8b-S43/N790) required for dsRNA binding, and key N-glycosylation sites (N138/N189) and cysteines (C3/C4/C6/C7) in CiTLR8a responsible for its proviral functions, with Cys6/Cys7 being critical for CiTLR8a/b proper localization. TLR8 evolution follows a stepwise pattern: absent in cyclostomes, it emerges in jawed vertebrates and expands via lineage-specific duplications (whole-genome in teleosts; tandem in amphibians/reptiles), is lost in avians, and persists as a single copy in mammals. Notably, Cyprinid TLR8 can bind dsRNA besides ssRNA. Collectively, our findings elucidate the functions, adaptive mechanisms, and evolutionary trajectory of TLR8 in lower vertebrates, uncovering a unique regulatory system involving its two homologs. These results offer a new perspective on how TLR evolution shapes vertebrate immune system. - Source: PubMed
Publication date: 2026/06/04
Zhang JingjingLv MaolinWang ShijieXu YuezongWang PengxuTang BoLiao ZhiweiJiang RuiChen GuanyuXiong NingxiaYang ChunrongLiu JingxiaSu Jianguo - Monocyte-macrophage lineage cells, crucial components of the innate immune system, can uniquely form bone-resorbing osteoclasts upon exposure to the cytokine receptor activator of nuclear factor κB ligand (RANKL) in the bone microenvironment. Recent studies have also begun to uncover extensive extraskeletal roles of RANKL. However, how monocyte-macrophage lineage cells respond to RANKL outside of the bone, and the impact that this signaling pathway exerts on the host immune response, is not fully understood. In this study, we sought to define how RANKL exposure shapes the macrophage inflammatory response to pathogens by using the model intracellular bacterium Salmonella enterica serovar Typhimurium, which coopts macrophages to cause life-threatening infections. We found that exposing both mouse and human macrophages to subosteoclastogenic levels of RANKL increased intracellular Salmonella enterica serovar Typhimurium burdens and decreased proinflammatory cytokine production. RNA sequencing revealed downregulation of pattern recognition receptor signaling pathways in RANKL-treated macrophages during the early stages of infection. Therefore, we hypothesized that RANKL impairs pattern recognition receptor-dependent signaling pathways that are important for proinflammatory cytokine production. We discovered that RANKL-treated macrophages exhibit reduced nuclear factor κB and interferon regulatory factor 3 activation, specifically in response to Toll-like receptor 2 (TLR2) and TLR4 stimulation. We determined that prior RANKL exposure decreases abundance of the TLR2 and TLR4 adaptor proteins TRAM (TRIF-related adaptor molecule) and TIRAP (TIR domain-containing adaptor protein). Together, these data suggest that RANKL exposure negatively impacts the macrophage TLR-mediated inflammatory response to bacteria. - Source: PubMed
Si Clara DPeek Christopher TFatah Sana RBeaudoin Andrew JZhelonkin Anton REichelberger Kara RHahn Stacy LWatson Robert OMogilenko Denis ACassat James E - Pyroptosis, a form of inflammatory programmed cell death, plays a dual role in tumor progression and anti-tumor immunity. Its comprehensive clinical and biological significance in intrahepatic cholangiocarcinoma (iCCA) remains to be elucidated. - Source: PubMed
Publication date: 2026/05/07
Zhao BinhanZhu YongjiJin ZiyangLi XiangLin KainanWang YifanLu YunkunHua Wen - This study investigates the systemic effects of amoxicillin and tetracycline on healthy Mus musculus (Swiss albino) mice, focusing on food intake, body weight, and hematological parameters. Over a 14-day oral treatment period, both antibiotics significantly reduced weight gain and food efficiency, with sex-specific variations: tetracycline had stronger metabolic effects in males, while amoxicillin was more impactful in females. To explore underlying mechanisms, molecular docking and MM-GBSA analyses were performed on PPAR-γ and TLR2-TIRAP complexes. Both antibiotics showed negligible binding to PPAR-γ, suggesting their metabolic effects are not receptor-mediated. In contrast, tetracycline exhibited strong and stable binding to TLR2 (ΔG = -27.87 kcal/mol), supported by extensive hydrogen bonding, implying potential immunomodulatory action. These findings suggest that antibiotic-induced metabolic and immune alterations are more likely driven by microbiota disruption and innate immune signaling, rather than direct metabolic receptor engagement. - Source: PubMed
Publication date: 2026/03/10
Mazreku IlirKasolli AulonGerxhaliu ZanaSmaili MelekBerisha AvniKaya SavaşMorales-Bayuelo Alejandro - Inflammation and endothelial dysfunction are key steps in the pathogenesis of atherosclerosis. Octacosanol (CHO, OCT), a very-long-chain saturated aliphatic alcohol (VLCA) with 28 carbons, is the main component of policosanol, a nutraceutical mixture of VLCAs (C20-C34) extracted from plants. Polycosanol in animal models is known to reduce atherosclerosis, but its mechanism of action remains unclear. This study investigates the pathways by which OCT alleviates LPS-induced inflammation in primary human aortic endothelial cells (HAECs). After overnight pretreatment with purified OCT, inflammation in HAECs was induced by lipopolysaccharide (LPS) at 100 ng/ml. The effects of OCT on the levels of pro-inflammatory cytokines, and molecules involved in inflammation signaling pathway, cell adhesion, and cell integrity were examined using quantitative RT-PCR, enzyme-linked immunosorbent assay, flow cytometry, or confocal microscopy in LPS-stimulated HAECs. The group of untreated HAECs was used as a control. OCT pretreatment of HAECs significantly reduced LPS-induced inflammatory responses, decreasing levels of IL-6, IL-8, and MCP-1 mRNA and protein, as well as TLR4, MYD88, TIRAP, TRAF6, and IRAK1 mRNA (p < 0.05). In a monocyte adhesion assay, LPS exposure increased human monocytic cells (THP-1) adherence to HAECs, whereas OCT pretreatment suppressed the LPS-induced adhesion of THP-1 to HAECs in a time- and dose-dependent manner, by blocking the mRNA and protein expression of adhesion molecules (VCAM-1, ICAM-1, P- and E-SELECTIN) (p < 0.05). OCT also suppressed mRNA and protein levels of CORTACTIN, VINCULIN, and TALIN, and inhibited focal adhesion and lamellipodia formation, cell deformation, and migration in response to LPS (p < 0.05). In addition, an endothelial permeability assay revealed that OCT pretreatment also improved endothelial cell integrity after LPS stimulation by preserving both adherens junctions and tight junctions formed by VE-CADHERIN, β -CATENIN, and Zonula Occludens-1 (ZO-1) (p < 0.05). In summary, the multiple cytoprotective effects of OCT against LPS-induced inflammation in endothelial cells could contribute to the anti-atherogenic properties of policosanol. - Source: PubMed
Publication date: 2026/02/11
Tang JingrongYang Zhi-HongLi WenlingLiu HuaitianLucero DiegoSviridov DenisWhite OliviaKun JuliaMukouyama Yoh-SukeRemaley Alan T