Hepatitis B Virus e Antigen Downregulates Cytokine Production in Human Hepatoma Cell Lines
Hepatitis B Virus e Antigen Downregulates Cytokine Production in Human Hepatoma Cell Lines
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DOI：
10.1089/vim.2010.0042
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发表时间：
2010-10-01
期刊：
影响因子：
2.2
通讯作者：
Yokosuka, Osamu
中科院分区：
文献类型：
--
作者：
Wu, Shuang;Kanda, Tatsuo;Yokosuka, Osamu
B型肝炎的疾病活动性受B型肝炎e抗原（HBeAg）状态的影响。B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不是病毒组装、感染或复制所必需的。我们研究了HBeAg和免疫系统的相互作用，包括细胞因子的产生。与HBeAg阴性HepG 2细胞相比，稳定表达HBeAg的HBeAg阳性HepG 2细胞中的炎性细胞因子TNF、IL-6、IL-8、IL-12 A、IFN-α 1和IFN-β mRNA下调。实时荧光定量RT-PCR相关基因芯片的结果显示，细胞因子和IFN的产生下调。我们还观察到在HBeAg阳性的HepG 2中NF-κ B和IFN-β启动子的激活的抑制，以及在HBeAg阳性的HepG 2细胞培养液中IFN和IL-6产生的抑制。HBeAg可能通过抑制炎性细胞因子和IFN基因表达，同时抑制NF-κ B信号传导和IFN-β启动子激活来改变疾病进展。
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-alpha 1, and IFN-beta 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-kappa B-and IFN-beta-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-kappa B-signaling- and IFNb-beta promoter activation.