Toll-like receptor 4 signalling: new perspectives on a complex signal-transduction problem.
Toll-like receptor 4 signalling: new perspectives on a complex signal-transduction problem.
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DOI：
10.1042/bst0310664
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发表时间：
2003-06
影响因子：
3.9
通讯作者：
S. Vogel;M. Fenton
中科院分区：
文献类型：
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作者：
S. Vogel;M. Fenton
我们以前报道，Toll样受体-2（TLR 2）激动剂比TLR 4激动剂诱导更有限的促炎基因库的表达。用TLR 4激动剂、大肠杆菌脂多糖刺激的鼠巨噬细胞诱导信号转导子和转录激活子1（“STAT 1”）酪氨酸磷酸化，其继发于干扰素（IFN）-β（一种立即早期基因）的自分泌/旁分泌作用。相反，TLR 2激动剂不能激活IFN-β基因表达。TLR 4诱导的IFN-β mRNA被发现是MyD 88和PKR（双链RNA依赖性蛋白激酶）非依赖性的，但TIRAP（Toll/白细胞介素-1受体结构域包含衔接蛋白）/Mal（MyD 88-衔接子样）依赖性的。在本文中，我们概述了最近的争议TIRAP/Mal在TLR 2和TLR 4信号转导的作用，在目前的分子工具用于此类研究的背景下。总的来说，我们的研究结果提供了第一个机制的基础上，TLR 4和TLR 2激动剂激活的基因表达的差异模式。
We previously reported that Toll-like receptor-2 (TLR2) agonists induce expression of a more limited repertoire of pro-inflammatory genes than TLR4 agonists. Murine macrophages stimulated with the TLR4 agonist, Escherichia coli lipopolysaccharide, induced signal transducer and activator of transcription 1 ('STAT1') tyrosine phosphorylation that was secondary to the autocrine/paracrine action of interferon (IFN)-beta, an immediate early gene. In contrast, TLR2 agonists failed to activate IFN-beta gene expression. TLR4-induced IFN-beta mRNA was found to be MyD88- and PKR (double-stranded RNA-dependent protein kinase)-independent, but TIRAP (Toll/interleukin-1 receptor domain-containing adapter protein)/Mal (MyD88-adapter-like)-dependent. In the present paper, we outline the recent controversy over the role of TIRAP/Mal in TLR2 and TLR4 signalling in the context of the current molecular tools used for such studies. Collectively, our findings provide the first mechanistic basis for differential patterns of gene expression activated by TLR4 and TLR2 agonists.