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首页> 外文期刊>Journal of endotoxin research >Interferon response induced by Toll-like receptor signaling.
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Interferon response induced by Toll-like receptor signaling.

机译:Toll样受体信号传导诱导的干扰素应答。

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Toll-like receptors (TLRs) are essential for the recognition of distinct pathogen-associated molecular patterns (PAMPs). Activation of TLRs induces intracellular signaling pathways which lead to the production of pro-inflammatory cytokines, chemokines, and interferon (IFN)-inducible genes. TIR domain containing adaptor molecules in turn determine the signaling specificity of the response. Recent studies demonstrated that serine/threonine kinases IKK-i/TBK1 are critical for the regulation of IFN-beta as well as IFN-inducible genes. In response to lipopolysaccharide (LPS), transfection of poly(I:C) and viral infection, embryonic fibroblasts (MEFs) derived from TBK1-deficient (TBK1-/-) mice show impaired production of IFN-inducible genes, but not proinflammatory cytokines. Although IKK-i-/- mice show normal production of these genes, MEFs from IKK-i/TBK1-doubly deficient mice were completely defective in the induction of IFN-beta as well as IFN-inducible genes in response to poly(I:C) stimulation. Activation of IFN-regulatory factor (IRF) 3 in response to LPS and poly(I:C) was abolished in IKK-i/TBK1 doubly deficient cells. Interestingly, intracellular transduction of poly(I:C) initiates activation of IFN response in a TLR3-independent manner. These observations demonstrate that IKK-i/TBK1 signaling is essential for both TLR3-dependent and TLR3-independent viral and dsRNA-induced IFN responses.
机译:Toll样受体(TLR)对于识别不同的病原体相关分子模式(PAMPs)是必不可少的。 TLR的激活诱导细胞内信号传导途径,从而导致促炎性细胞因子,趋化因子和干扰素(IFN)诱导型基因的产生。含有TIR结构域的衔接子分子又决定了反应的信号传导特异性。最近的研究表明,丝氨酸/苏氨酸激酶IKK-1 / TBK1对于调节IFN-β以及IFN诱导型基因至关重要。响应脂多糖(LPS),聚(I:C)的转染和病毒感染,源自TBK1缺陷(TBK1-/-)小鼠的胚胎成纤维细胞(MEF)显示出IFN诱导型基因的产生受损,但促炎性细胞因子未受损。尽管IKK-i-/-小鼠显示出这些基因的正常产生,但来自IKK-i / TBK1双重缺陷小鼠的MEF在诱导IFN-β以及响应于poly(I: C)刺激。在IKK-1 / TBK1双倍缺乏的细胞中,取消了针对LPS和poly(I:C)的IFN-调节因子(IRF)3的激活。有趣的是,poly(I:C)的细胞内转导以TLR3独立的方式启动IFN反应的激活。这些观察结果表明,IKK-1 / TBK1信号传导对于TLR3依赖性和TLR3依赖性病毒和dsRNA诱导的IFN反应都是必不可少的。

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