乙型肝炎病毒表面抗原抑制TLR2和TLR4的激活  

HBsAg interferes with the TLR2 and TLR4 signaling pathway

作　　者：刘华[1] 陈志翱[1] 成玉明[1] 袁正宏[1] 

机构地区：[1]复旦大学上海医学院教育部/卫生部医学分子病毒学重点实验室,上海200032

出　　处：《微生物与感染》2008年第2期84-89,117,共7页Journal of Microbes and Infections

基　　金：国家863高科技项目(NoKSF113007)

摘　　要：目的研究乙型肝炎病毒表面抗原(HBsAg)在乙型肝炎病毒(HBV)逃逸机体天然免疫中的作用。方法用乙酸肉豆蔻佛波酯(PMA)诱导人单核细胞白血病细胞(THP)-1分化成巨噬样细胞,并与HBsAg共培养作比较,在脂多糖(LPS,TLR4的配体)和Pam3CSK4(TLR1、2的配体)的刺激下,检测细胞上清液中细胞因子白细胞介素10(IL-10)、IL-12的表达及胞内IL-10、IL-12mRNA的含量,并利用免疫荧光法观察核转录因子-kappaB(NF-κB)p65入核和蛋白质印迹法(Western blot)检测IκB-α蛋白降解与胞外信号调节激酶(ERK)蛋白磷酸化水平来判定TLR信号通路活化程度。结果HBsAg的胞外处理能以剂量依赖的方式干扰Pam3CSK4和LPS诱导的IL-10和IL-12的产生,同时HBsAg的存在明显干扰Pam3CSK4和LPS诱导的NF-κB p65入核和IκB-α降解以及ERK蛋白磷酸化水平。结论HBsAg抑制TLR2和TLR4的激活。Objective To investigate the role of hepatitis B surface antigen （HBsAg） in the escape of the by hepatitis B virus （HBV） from the innate i mmunity.Mellmds After treated with PMA, THP-1 cells diferenfiated into macrophage-like cells. Macrophage-like cells were further treated with LPS and the Pam3CSK4 in the presence or absence of HBsAg. Cytokine IL-10,IL-12 protein,IL-10,IL-12 mRNA levels, NF-κB p65 protein nuclear translocation, κB-α degradation and ERK protein phosphorylation were detected to monitor the activation of the TLR signaling pathway.Results LPS and Pam3CSK4-induced production of cytokine IL-10, IL-12, NF-αB p65 protein nuclear trannslocation.Furthermore κB-α degradation and ERK protein phosphorylation were inhibited by HBsAg in a dose-dependent manner. Conclusion HBsAg inhibits the activation of TLR2 and TLR4 signaling pathway.

关 键 词：乙型肝炎病毒表面抗原 TOLL样受体 巨噬样细胞 人单核细胞白血病细胞-1 

分 类 号：R392[医药卫生—免疫学]