title: Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes.
abstract: 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-κB (NF-κB) and production of interleukin-6 (IL-6), IL-8, and CXCL2. These findings suggest that autophagy is required for HBx-induced NF-κB activation and pro-inflammatory cytokine production and could shed new light on the complex role of autophagy in the modulation of inflammation.
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Millore X M
authors.initials: MX
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Sunny H
authors.initials: SH
authors.lastname: Wong
authors.affiliation: Department of Anaesthesia & Intensive Care, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Matthew T V
authors.initials: MT
authors.lastname: Chan
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Le
authors.initials: L
authors.lastname: Yu
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Sidney S B
authors.initials: SS
authors.lastname: Yu
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Zhangang
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.|School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Alfred S L
authors.initials: AS
authors.lastname: Cheng
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Simon S M
authors.initials: SS
authors.lastname: Ng
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Francis K L
authors.initials: FK
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.|School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Chi H
authors.initials: CH
authors.lastname: Cho
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.affiliation: State Key Laboratory of Digestive Diseases, Institute of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.|Department of Anaesthesia & Intensive Care, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: William K K
authors.initials: WK
authors.lastname: Wu
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D054426:Chemokine CXCL2 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006515:Hepatitis B virus / Q000302:isolation & purification*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C499706:CXCL2 protein, human; C508606:CXCL8 protein, human; D054426:Chemokine CXCL2; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein