Department of Medicine and Clinical Oncology, Chiba University, Graduate School of Medicine, Chiba, Japan.
Viral Immunol. 2010 Oct;23(5):467-76. doi: 10.1089/vim.2010.0042.
Disease activities of hepatitis B are affected by the status of hepatitis B e antigen (HBeAg). The function of the hepatitis B virus (HBV) precore or HBeAg is unknown. We assumed that HBeAg blocks aberrant immune responses, although HBeAg is not required for viral assembly, infection, or replication. We examined the interaction of HBeAg and the immune system, including cytokine production. The inflammatory cytokine TNF, IL-6, IL-8, IL-12A, IFN-α1, and IFN-ß mRNA were downregulated in HBeAg-positive HepG2, which stably expresses HBeAg, compared to HBeAg-negative HepG2 cells. The results of real-time RT-PCR-based cytokine-related gene arrays showed the downregulation of cytokine and IFN production. We also observed inhibition of the activation of NF-κB- and IFN-ß-promoter in HBeAg-positive HepG2, as well as inhibition of IFN and IL-6 production in HBeAg-positive HepG2 cell culture fluids. HBeAg might modify disease progression by inhibiting inflammatory cytokine and IFN gene expression, while simultaneously suppressing NF-κB-signaling- and IFNß-promoter activation.
乙型肝炎的疾病活动受到乙型肝炎 e 抗原 (HBeAg) 的状态影响。乙型肝炎病毒 (HBV) 前核心或 HBeAg 的功能尚不清楚。我们假设 HBeAg 阻断异常的免疫反应，尽管 HBeAg 对于病毒装配、感染或复制并非必需。我们研究了 HBeAg 与免疫系统的相互作用，包括细胞因子的产生。与 HBeAg 阴性 HepG2 细胞相比，稳定表达 HBeAg 的 HBeAg 阳性 HepG2 细胞中炎性细胞因子 TNF、IL-6、IL-8、IL-12A、IFN-α1 和 IFN-ß mRNA 的表达下调。基于实时 RT-PCR 的细胞因子相关基因芯片的结果显示细胞因子和 IFN 产生受到抑制。我们还观察到 HBeAg 阳性 HepG2 中 NF-κB-和 IFN-ß-启动子的激活受到抑制，以及 HBeAg 阳性 HepG2 细胞培养物中 IFN 和 IL-6 产生受到抑制。HBeAg 可能通过抑制炎症细胞因子和 IFN 基因表达，同时抑制 NF-κB-信号和 IFNβ-启动子激活，从而改变疾病进展。
