乙型肝炎病毒及其核心抗原对巨噬细胞极化的影响  

Effect of hepatitis B virus and hepatitis B core antigen on macrophage polarization

作　　者：伊宏煜 张津睿 胡海峰 张野 陈丽华(指导) 连建奇(指导) YI Hong-Yu;ZHANG Jin-Rui;HU Hai-Feng;ZHANG Ye;CHEN Li-Hua;LIAN Jian-Qi(Center for Infectious Diseases,Tangdu Hospital,Air Force Military Medical University,Xi′an 710032,China)

机构地区：[1]空军军医大学唐都医院传染病科,西安710032 [2]空军军医大学基础医学院学员五大队,西安710032 [3]空军军医大学基础医学院免疫学教研室,西安710032

出　　处：《中国免疫学杂志》2020年第7期769-773,共5页Chinese Journal of Immunology

基　　金：“十三五”传染病重大专项子课题(2017ZX10204401-002-005);国家自然科学基金项目(81571531)和陕西省重点研发计划(2018SF-139)资助。

摘　　要：目的:探讨乙型肝炎病毒(HBV)和乙型肝炎核心抗原(HBcAg)对巨噬细胞M1/M2极化的影响。方法:体外培养人白血病单核细胞系THP-1,用佛波酯将其诱导为人巨噬细胞,然后分别与HepG2/HepG2.2.15细胞和HBcAg共培养。通过流式细胞术观察共培养后THP-1巨噬细胞极化相关分子的变化;收集细胞培养上清,用ELISA检测巨噬细胞中促炎和抗炎细胞因子的分泌水平;应用RT-qPCR检测共培养后巨噬细胞极化相关分子和细胞因子的表达水平。结果:与HepG2细胞对照组相比,分泌HBV的HepG2.2.15细胞与THP-1巨噬细胞共培养能够上调其CD86和CCR7表达水平,同时促进IL-6、TNF-α和IL-10的分泌。而与HBcAg共培养后,THP-1巨噬细胞上CD163、CD206以及CD86表达水平升高,同时促进TGF-β、IL-10和TNF-α的分泌。结论:①HBV主要促进THP-1巨噬细胞向促炎的M1方向极化;②HBcAg主要促进THP-1巨噬细胞向抑炎的M2方向极化但同时也影响THP-1巨噬细胞向M1方向的极化。Objective:To investigate the effects of hepatitis B virus(HBV)and hepatitis B core antigen(HBcAg)on the M1/M2 polarization phenotype of macrophages.Methods:Human leukemia monocytic cell line THP-1 was cultured in vitro and differentiated into human macrophages by phorbol ester,and then co-cultured with HepG2/HepG2.2.15 cells and HBcAg,respectively.Flow cytometry was used to observe the changes of macrophage polarization-related molecules of THP-1 after co-culture.The supernatant of cultured cells was collected,and the levels of pro-inflammatory and anti-inflammatory cytokines secreted by macrophages were detected by ELISA.The expression of polarization-related molecules and cytokines of macrophages after co-culture were detected by RT-qPCR.Results:HBV-secreted HepG2.2.15 cells up-regulated the expression of CD86 and CCR7 of THP-1,while promoted the secretion of IL-6,TNF-αand IL-10 compared with HepG2 cells.When co-cultured with HBcAg,the expression of CD163,CD206 and CD86 were up-regulated in THP-1 cells,and the secretion of TGF-β,IL-10 and TNF-αwere also promoted.Conclusion:①HBV mainly promotes the polarization of macrophages towards the pro-inflammatory M1 phenotype.②HBcAg mainly promotes the polarization of macrophages towards the anti-inflammatory M2 phenotype while affects the polarization of macrophages towards M1 phenotype.

关 键 词：乙型肝炎病毒 乙肝核心抗原 巨噬细胞 极化 

分 类 号：R392.9[医药卫生—免疫学]