Essential role of IRF-3 in lipopolysaccharide-induced interferon-β gene expression and endotoxin shock
Essential role of IRF-3 in lipopolysaccharide-induced interferon-β gene expression and endotoxin shock
复制标题
DOI：
10.1016/s0006-291x(03)01049-0
复制
发表时间：
2003-07-11
影响因子：
3.1
通讯作者：
Taniguchi, T
中科院分区：
文献类型：
--
作者：
Sakaguchi, S;Negishi, H;Taniguchi, T
I型干扰素（IFN-α/β）影响免疫应答的许多方面。许多病原体相关分子，包括细菌脂多糖（LPS）和病毒相关的双链RNA，通过激活不同的Toll样受体（TLR）诱导IFN基因表达。尽管已经研究了很多关于转录因子IRF-3的激活和通过LPS介导的TLR 4信号传导诱导IFN-β基因的研究，但是关于IRF-3在体外和体内LPS应答中的实际作用的确切证据缺失。使用IRF-3缺陷小鼠，我们在这里表明，IRF-3确实是必不可少的LPS介导的IFN-β基因诱导。IRF-3的缺失也影响其他细胞因子/趋化因子基因的表达谱。我们还提供了证据表明，LPS/TLR 4信号激活IRF-7诱导IFN-β，如果IRF-7诱导的IFN前LPS刺激。最后，IRF-3缺陷型小鼠显示出对LPS诱导的内毒素休克的抗性。这些结果将IRF-3作为LPS/TLR 4信号传导的中心分子。(C)2003 Elsevier Science（美国）。All rights reserved.
Type I interferons (IFN-alpha/beta) affect many aspects of immune responses. Many pathogen-associated molecules, including bacterial lipopolysaccharide (LPS) and virus-associated double-stranded RNA, induce IFN gene expression through activation of distinct Toll-like receptors (TLRs). Although much has been studied about the activation of the transcription factor IRF-3 and induction of IFN-beta gene by the LPS-mediated TLR4 signaling, definitive evidence is missing about the actual role of IRF-3 in LPS responses in vitro and in vivo. Using IRF-3 deficient mice, we show here that IRF-3 is indeed essential for the LPS-mediated IFN-beta gene induction. Loss of IRF-3 also affects the expression of profile of other cytokine/chemokine genes. We also provide evidence that the LPS/TLR4 signaling activates IRF-7 to induce IFN-beta, if IRF-7 is induced by IFNs prior to LPS simulation. Finally, the IRF-3-deficient mice show resistance to LPS-induced endotoxin shock. These results place IRF-3 as a molecule central to LPS/TLR4 signaling. (C) 2003 Elsevier Science (USA). All rights reserved.