發(fā)布時(shí)間：2018-02-28 20:19

  本文關(guān)鍵詞： 蛋白磷酸酶PPCB 天然免疫 Ⅰ型干擾素 巨噬細(xì)胞　出處：《中國免疫學(xué)雜志》2017年06期 　論文類型：期刊論文

【摘要】：目的:研究蛋白磷酸酶PP2CB在抗RNA病毒天然免疫應(yīng)答中的調(diào)控作用及其機(jī)制。方法:在小鼠腹腔巨噬細(xì)胞中轉(zhuǎn)染PP2CB的特異siRNA,干擾其表達(dá)后通過Q-PCR和ELISA觀察RNA病毒誘導(dǎo)的Ⅰ型干擾素的產(chǎn)生變化、病毒在細(xì)胞內(nèi)的復(fù)制變化,Western blot檢測TBK1和IRF3的磷酸化水平的改變。結(jié)果:VSV感染誘導(dǎo)巨噬細(xì)胞中PP2CB的表達(dá)發(fā)生顯著改變。過表達(dá)PP2CB抑制HEK293細(xì)胞中IFN-β的轉(zhuǎn)錄活化。干擾PP2CB表達(dá)顯著升高RNA病毒VSV或SeV誘導(dǎo)的Ⅰ型干擾素的mRNA和蛋白表達(dá)水平,并抑制VSV復(fù)制。此外,RNA病毒誘導(dǎo)PP2CB和TBK1結(jié)合。干擾PP2CB的表達(dá)能夠增強(qiáng)TBK1和IRF3的磷酸化。結(jié)論:RNA病毒VSV或SeV使蛋白磷酸酶PP2CB能夠結(jié)合TBK1并抑制其磷酸化,下調(diào)Ⅰ型干擾素信號(hào)通路的活化,從而負(fù)向調(diào)控RNA病毒VSV或SeV誘導(dǎo)的Ⅰ型干擾素的產(chǎn)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.
【作者單位】： 第二軍醫(yī)大學(xué)免疫學(xué)研究所暨醫(yī)學(xué)免疫學(xué)國家重點(diǎn)實(shí)驗(yàn)室;
【基金】：國家自然科學(xué)基金優(yōu)秀青年科學(xué)基金(81422021)資助
【分類號(hào)】：R392
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本文編號(hào)：1548798