Cutting edge:: A novel toll/IL-1 receptor Domain containing adapter that preferentially activates the IFN-β promoter in the toll-like receptor signaling
Cutting edge:: A novel toll/IL-1 receptor Domain containing adapter that preferentially activates the IFN-β promoter in the toll-like receptor signaling
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DOI：
10.4049/jimmunol.169.12.6668
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发表时间：
2002-12-15
影响因子：
4.4
通讯作者：
Akira, S
中科院分区：
文献类型：
--
作者：
Yamamoto, M;Sato, S;Akira, S
MyD 88是Toll/IL-1受体（TIR）结构域的衔接子，其与通过Toll样受体（TLR）家族的信号传导途径共有。然而，越来越多的证据表明存在一个MyD 88独立的途径，这可能会解释独特的生物反应的个别TLR，特别是TLR 3和TLR 4。含有TIR结构域的衔接蛋白（TIRAP）/MyD 88衔接子样，第二个含有TIR结构域的衔接子，对于MyD 88依赖的TLR 2和TLR 4信号通路是必需的，但对于MyD 88非依赖的通路不是必需的。在这里，我们确定了一种新的TIR结构域的分子，命名为TIR结构域的适配器诱导IFN-β（TRIF）。与MyD 88和TIRAP的情况一样，TRIF的过表达激活了NF-κ B依赖性启动子。TRIF的显性阴性形式抑制TLR 2-、TLR 4-和TLR 7-依赖性NF-κ B活化。此外，TRIF激活IFN-β启动子，而MyD 88和TIRAP均未激活。显性负性TRIF抑制NF-κ B依赖性和IFN-β启动子的TLR 3依赖性活化。TRIF与TLR 3和IFN调节因子3相关。这些发现表明TRIF参与TLR信号传导，特别是在MyD 88非依赖性途径中。
MyD88 is a Toll/IL-1 receptor (TIR) domain-containing adapter common to signaling pathways via Toll-like receptor (TLR) family. However, accumulating evidence demonstrates the existence of a MyD88-independent pathway, which may explain unique biological responses of individual TLRs, particularly TLR3 and TLR4. TIR domain-containing adapter protein (TIRAP)/MyD88 adapter-like, a second adapter harboring the TIR domain, is essential for MyD88-dependent TLR2 and TLR4 signaling pathways, but not for MyD88-independent pathways. Here, we identified a novel TIR domain-containing molecule, named TIR domain-containing adapter inducing IFN-beta (TRIF). As is the case in MyD88 and TIRAP, overexpression of TRIF activated the NF-kappaB-dependent promoter. A dominant-negative form of TRIF inhibited TLR2-, TLR4-, and TLR7-dependent NF-kappaB activation. Furthermore, TRIF, but neither MyD88 nor TIRAP, activated the IFN-beta promoter. Dominant-negative TRIF inhibited TLR3-dependent activation of both the NF-kappaB-dependent and IFN-beta promoters. TRIF associated with TLR3 and IFN regulatory factor 3. These findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway.