Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes
Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes
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DOI：
10.1002/jcp.24967
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发表时间：
2015-10-01
影响因子：
5.6
通讯作者：
Wu, William K. K.
中科院分区：
文献类型：
--
作者：
Luo, Millore X. M.;Wong, Sunny H.;Wu, William K. K.
B型肝炎病毒（HBV）及其编码蛋白HBVX蛋白（HBx）可诱导肝癌细胞自噬。大量证据表明，自噬是一种有效的炎症抑制剂。然而，零星的报告表明，自噬可以促进促炎细胞因子的表达和炎症在一些生物学背景下。在这里，我们发现HBx的过度表达诱导LC 3B阳性自噬体形成，增加自噬通量，并增强正常肝细胞中ATG 5，ATG 7和LC 3B-II的表达。通过针对ATG 5和ATG 7的小干扰RNA消除自噬阻止HBx诱导的自噬体的形成。自噬抑制还消除了HBx诱导的核因子-κ B（NF-κ B）活化和白细胞介素-6（IL-6）、IL-8和CXCL 2的产生。这些发现表明，自噬是HBx诱导的NF-κ B活化和促炎细胞因子产生所必需的，并且可以揭示自噬在炎症调节中的复杂作用。(C)2015 Wiley Periodicals，Inc.
Hepatitis B virus (HBV) and one of its encoded proteins, HBV X protein (HBx), have been shown to induce autophagy in hepatoma cells. Substantial evidence indicates that autophagy is a potent suppressor of inflammation. However, sporadic reports suggest that autophagy could promote pro-inflammatory cytokine expression and inflammation in some biological contexts. Here, we show that overexpression of HBx induces LC3B-positive autophagosome formation, increases autophagic flux and enhances the expression of ATG5, ATG7, and LC3B-II in normal hepatocytes. Abrogation of autophagy by small interfering RNA against ATG5 and ATG7 prevents HBx-induced formation of autophagosomes. Autophagy inhibition also abrogates HBx-induced activation of nuclear factor-kappa B (NF-kappa B) and production of interleukin-6 (IL-6), IL-8, and CXCL2. These findings suggest that autophagy is required for HBx-induced NF-kappa B activation and pro-inflammatory cytokine production and could shed new light on the complex role of autophagy in the modulation of inflammation. (C) 2015 Wiley Periodicals, Inc.