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USP14 negatively regulates RIG-I-mediated IL-6 and TNF-α production by inhibiting NF-κB activation
Molecular Immunology ( IF 3.6 ) Pub Date : 2020-12-23 , DOI: 10.1016/j.molimm.2020.12.022
Hongrui Li , Jiazheng Quan , Xibao Zhao , Jing Ling , Weilin Chen

Ubiquitin specific protease 14 (USP14) is a regulator of protein deubiquitination and proteasome activation, and has been implicated in negative regulation of type I IFN signaling pathway. However, the effect of USP14 on RNA virus-related inflammatory response has not been studied. Retinoic acid-inducible gene I (RIG-I) is the important pattern recognition receptor of the innate immunity to detect RNA viruses or intracellular Poly(I:C)-LMW. Here, we reported that USP14 knockdown increased pro-inflammatory cytokines production in macrophages upon VSV infection or intracellular Poly(I:C)-LMW stimulation. USP14-overexpressed HeLa cells exhibited a decrease in RIG-I-mediated IL-6 and TNF-α expression. IU1, USP14 inhibitor, significantly promotes pro-inflammatory cytokines production in VSV-infected mice in vivo. Furthermore, USP14 was also found to inhibit the RIG-I-triggered NF-κB activation by deubiquitinating K63-linked RIG-I. Thus, our results demonstrate that USP14 is a negative regulator of RIG-I-mediated inflammatory response.



中文翻译:

USP14通过抑制NF-κB活化来负调节RIG-I介导的IL-6和TNF-α的产生

泛素特异性蛋白酶14(USP14)是蛋白质去泛素化和蛋白酶体激活的调节剂,并已参与I型IFN信号通路的负调节。但是,尚未研究过USP14对RNA病毒相关炎症反应的影响。维甲酸诱导基因I(RIG-I)是先天免疫的重要模式识别受体,可检测RNA病毒或细胞内Poly(I:C)-LMW。在这里,我们报道说,USP14基因敲低增加了VSV感染或细胞内Poly(I:C)-LMW刺激后巨噬细胞中促炎性细胞因子的产生。USP14过度表达的HeLa细胞在RIG-I介导的IL-6和TNF-α表达上降低。USP14抑制剂IU1在体内显着促进受VSV感染的小鼠体内促炎性细胞因子的产生。此外,USP14还被发现通过去泛素化K63连接的RIG-I来抑制RIG-I触发的NF-κB活化。因此,我们的结果证明USP14是RIG-I介导的炎症反应的负调节剂。

更新日期:2020-12-23
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