组蛋白乙酰化修饰调控流感病毒复制中间体dsRNA引起的IL-6激活表达

Histone acetylation modulates influenza virus replicative intermediate dsRNA-induced interleukin-6 expression in A549 cells

目的研究组蛋白乙酰化修饰在流感病毒复制中间体dsRNA引起IL-6表达中的调控作用。方法以病毒复制中间体dsRNA为诱导物,利用组蛋白去乙酰化酶(HDAC)抑制剂、DNA甲基转移酶(DNMT)抑制剂或HDAC siRNA分别处理A549细胞,双荧光素酶报告系统分析IL-6启动子活性、RT-PCR检测mRNA转录水平以及ELISA检测蛋白表达。结果 dsRNA可激活IL-6启动子活性、增强mRNA转录水平和蛋白的分泌表达,用HDAC抑制剂TSA处理或HADC siRNA干扰均可显著增强IL-6启动子活性和mRNA转录,同时,HDAC抑制剂TSA和DNA甲基转移酶抑制剂DAC在调控IL-6表达过程中无协同作用。结论在流感病毒复制中间体dsRNA引起IL-6表达上调过程中受到组蛋白乙酰化修饰调控。

Objective To investigate the role of histone acetylation in regulating influenza virus replicative intermediate double-stranded RNA （dsRNA）-induced interleukin-6 （IL-6） expression in A549 cells. Methods A549 cells were treated with influenza virus replicatlve intermediate dsRNA, histone deacetylase （HDAC） inhibitor trichostafin A （TSA）, or HADC small interfering RNA （siRNA）. The changes in the cellular IL-6 promoter activities were detected by dual-luciferase assa~ and IL-6 mRNA and protein expressions in the ceils were determined using real-time RT-PCR and ELISA, respectively. Results Influenza virus replicative intermediate dsRNA obviously up-regulated IL-6 expression in the cells. HDAC inhibitor TSA significantly enhanced the activity of IL-6 promoter and increased IL-6 mRNA expression in A549 cells, and HDAC3 may play an important role in this process. HDAC inhibitor TSA and DNMT inhibitor DAC showed no synergic effect in regulating IL-6 expression. Conclusion Influenza virus replicative intermediate dsRNA-induced IL-6 expression in A549 cells is regulated by histone acetylation.