TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF
TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF
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DOI：
10.1002/eji.200526151
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发表时间：
2005-08-01
影响因子：
5.4
通讯作者：
Suzuki, K
中科院分区：
文献类型：
--
作者：
Takeshita, F;Ishii, KJ;Suzuki, K
Toll样受体（TLR）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶在吞噬病原体的细胞内根除中起重要作用。在这里，我们证明了细胞溶质NADPH氧化酶和TLR介导的信号分子的组件之间的物理和功能关联。NADPH氧化酶的胞质组分抑制TLR介导的NF-κ B活化以及IFN-β启动子活化。我们证明，TNT相关因子（TRAF）4与p47（phox），胞质NADPH氧化酶的一个组成部分，物理相互作用和功能抵消TRAF 6和Toll-IL-1受体（TIR）域含有衔接子诱导IFN-β（TRIF）分子，关键调节TLR介导的信号。LPS或CpG DNA处理后，RPMI 8226细胞中TRAF 4 mRNA表达被诱导。这些结果表明，TRAF 4通过与携带吞噬体/内体膜的分子相互作用参与TLR介导的信号转导沉默的分子机制。
Toll-like receptors (TLR) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play an essential role in intracellular eradication of engulfed pathogens. Here, we demonstrate the physical and functional association between components of the cytosolic NADPH oxidase and TLR-mediated signaling molecules. Cytosolic components of NADPH oxidase suppressed TLR-mediated NF-kappa B activation as well as IFN-beta promoter activation. We demonstrate that TNT-associated factor (TRAF) 4 associates with p47(phox), a component of cytosolic NADPH oxidase, and physically interacts and functionally counteracts with TRAF6 and Toll-IL-1 receptor (TIR) domain-containing adaptor-inducing IFN-beta (TRIF) molecules that critically regulate TLR-mediated signaling. TRAF4 mRNA expression was elicited in RPMI 8226 cells following LPS or CpG DNA treatment. These results suggest that TRAF4 participates in the molecular mechanism underlying silencing of TLR-mediated signaling through the interaction with molecules harboring phagosome/endosome membrane.