Cutting Edge: Roles of Caspase-8 and Caspase-10 in Innate Immune Responses to Double-Stranded RNA
Cutting Edge: Roles of Caspase-8 and Caspase-10 in Innate Immune Responses to Double-Stranded RNA
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DOI：
10.4049/jimmunol.176.8.4520
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发表时间：
2006-04
期刊：
影响因子：
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通讯作者：
Ken Takahashi;T. Kawai;H. Kumar;Shintaro Sato;S. Yonehara;S. Akira
中科院分区：
文献类型：
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作者：
Ken Takahashi;T. Kawai;H. Kumar;Shintaro Sato;S. Yonehara;S. Akira
病毒感染后，宿主细胞通过诱导I型IFN和炎性细胞因子触发抗病毒免疫应答。病毒复制过程中产生的dsRNA被细胞质RNA解旋酶视黄酸诱导基因I和黑素瘤分化相关基因5识别，它们与接头IFN-β启动子刺激因子1相互作用，以激活转录因子NF-κB和IFN调节因子3。在这篇文章中，我们证明，caspase-8和caspase-10参与这些途径。在dsRNA刺激期间，两种半胱天冬酶都被切割，并且这些半胱天冬酶的切割形式的过表达激活NF-κB。人细胞系中半胱天冬酶-10或半胱天冬酶-8的敲低导致炎性细胞因子产生的减少。来自caspase-8缺陷小鼠的细胞也显示炎性细胞因子表达减少以及NF-κB活化。此外，Fas相关的死亡结构域蛋白与这两个半胱天冬酶和IFN-β启动子刺激因子1相互作用。这些结果表明，caspase-8和caspase-10是介导NF-κ B依赖性炎症反应的抗病毒信号转导的重要组成部分。
Upon viral infection, host cells trigger antiviral immune responses by inducing type I IFN and inflammatory cytokines. dsRNA generated during viral replication is recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, which interact with an adaptor, IFN-β promoter stimulator-1, to activate the transcription factors NF-κB and IFN regulatory factor 3. In this article we demonstrate that caspase-8 and caspase-10 are involved in these pathways. Both caspases were cleaved during dsRNA stimulation, and overexpression of a cleaved form of these caspases activated NF-κB. Knockdown of caspase-10 or caspase-8 in a human cell line resulted in the reduction of inflammatory cytokine production. Cells derived from caspase-8-deficient mice also showed reduced expression of inflammatory cytokines as well as NF-κB activation. Furthermore, the Fas-associated death domain protein interacted with these two caspases and IFN-β promoter stimulator 1. These results indicate that caspase-8 and caspase-10 are essential components that mediate NF-κB-dependent inflammatory responses in antiviral signaling.