Department of Infectious Diseases, The 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, People's Republic of China.
Mol Immunol. 2011 Jul;48(12-13):1573-7. doi: 10.1016/j.molimm.2011.03.012. Epub 2011 Apr 8.
HBV replicates noncytopathically in hepatocytes, but HBV or proteins encoded by HBV genome could induce cytokines, chemokines expression by hepatocytes. Moreover, liver damage in patients with HBV infection is immune-mediated and cytokines play important roles in immune-mediated liver damage after HBV infection. Interleukin-32 (IL-32) is a proinflammatory cytokine and plays a critical role in inflammation. However, the role of HBV in IL-32 expression remains unclear. In the present study, we demonstrate that hepatitis B virus protein X (HBx) increases IL-32 expression through the promoter of IL-32 at positions from -746 to +25 and in a dose-dependent manner. Furthermore, we demonstrate that increase of NF-κB subunits p65 and p50 in Huh7 cells also augments IL-32 expression, and the NF-κB inhibitor blocks the effect of HBx on IL-32 induction. These results indicate that NF-κB activation is required for HBx-induced IL-32 expression. In conclusion, IL-32 is induced by HBx in Huh7 cells. Our results suggest that IL-32 might play an important role in inflammatory response after HBV infection.
HBV 在肝细胞中非细胞病变地复制，但 HBV 或其基因组编码的蛋白质可诱导肝细胞表达细胞因子和趋化因子。此外，HBV 感染患者的肝损伤是免疫介导的，细胞因子在 HBV 感染后免疫介导的肝损伤中发挥重要作用。白细胞介素-32 (IL-32) 是一种促炎细胞因子，在炎症中发挥关键作用。然而，HBV 在 IL-32 表达中的作用尚不清楚。在本研究中，我们证明乙型肝炎病毒蛋白 X (HBx) 通过 IL-32 的启动子从-746 到+25 位以剂量依赖的方式增加 IL-32 的表达。此外，我们证明 NF-κB 亚基 p65 和 p50 在 Huh7 细胞中的增加也增强了 IL-32 的表达，并且 NF-κB 抑制剂阻断了 HBx 对 IL-32 诱导的作用。这些结果表明，NF-κB 的激活是 HBx 诱导 IL-32 表达所必需的。总之，HBx 在 Huh7 细胞中诱导了 IL-32 的表达。我们的结果表明，IL-32 可能在 HBV 感染后的炎症反应中发挥重要作用。
