磷酸酶PP2CB抑制RNA病毒VSV或SeV介导的天然免疫应答

发布时间：2018-02-28 20:19

  本文关键词： 蛋白磷酸酶PPCB 天然免疫 Ⅰ型干扰素 巨噬细胞　出处：《中国免疫学杂志》2017年06期 　论文类型：期刊论文

【摘要】：目的:研究蛋白磷酸酶PP2CB在抗RNA病毒天然免疫应答中的调控作用及其机制。方法:在小鼠腹腔巨噬细胞中转染PP2CB的特异siRNA,干扰其表达后通过Q-PCR和ELISA观察RNA病毒诱导的Ⅰ型干扰素的产生变化、病毒在细胞内的复制变化,Western blot检测TBK1和IRF3的磷酸化水平的改变。结果:VSV感染诱导巨噬细胞中PP2CB的表达发生显著改变。过表达PP2CB抑制HEK293细胞中IFN-β的转录活化。干扰PP2CB表达显著升高RNA病毒VSV或SeV诱导的Ⅰ型干扰素的mRNA和蛋白表达水平,并抑制VSV复制。此外,RNA病毒诱导PP2CB和TBK1结合。干扰PP2CB的表达能够增强TBK1和IRF3的磷酸化。结论:RNA病毒VSV或SeV使蛋白磷酸酶PP2CB能够结合TBK1并抑制其磷酸化,下调Ⅰ型干扰素信号通路的活化,从而负向调控RNA病毒VSV或SeV诱导的Ⅰ型干扰素的产生。
[Abstract]:Objective: to study the regulation and mechanism of protein phosphatase (PP2CB) in innate immune response to RNA virus. Methods: the specific siRNAs transfected with PP2CB in murine peritoneal macrophages were transfected with PP2CB and the expression of PP2CB was interfered with. Q-PCR and ELISA were used to observe the induction of RNA virus. Changes in the production of type I interferon, The changes of viral replication in cells and the changes of phosphorylation of TBK1 and IRF3 by Western blot. Results the expression of PP2CB in macrophages induced by the infection of 1: VSV was significantly changed. Overexpression of PP2CB inhibited the transcriptional activation of IFN- 尾 and interfered with the expression of IFN- 尾 in HEK293 cells. PP2CB expression significantly increased the expression of mRNA and protein in interferon type I induced by RNA virus VSV or SeV. In addition, interfering with the expression of PP2CB can enhance the phosphorylation of TBK1 and IRF3. Conclusion VSV or SeV can inhibit the phosphorylation and binding of protein phosphatase PP2CB to TBK1. The activation of type I interferon signaling pathway was down-regulated, which negatively regulated the production of type I interferon induced by RNA virus VSV or SeV.
【作者单位】： 第二军医大学免疫学研究所暨医学免疫学国家重点实验室;
【基金】：国家自然科学基金优秀青年科学基金(81422021)资助
【分类号】：R392
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本文编号：1548798