title: Hepatitis B Virus Core Antigen Stimulates IL-6 Expression via p38, ERK and NF-κB Pathways in Hepatocytes.
abstract: BACKGROUND
  Hepatitis B virus (HBV) causes both acute and chronic liver injury. Viral proteins are involved in the pathological progress. Hepatitis B core antigen (HBcAg), a component of viral nucleocapsid, is not only essential for HBV lifecycle, but also exhibits strong immunogenicity. The cytoplasmic location of HBcAg in liver biopsy is associated with liver injury and inflammation, but the exact mechanisms remain to be elaborated.
  
  
  METHODS
  Huh7, SMMC-7721 and L-02 cells were transfected with pEGFP-N1-HBcAg to establish an intracellular HBcAg expression model. The mRNA and protein levels of Interleukin (IL)-6 were detected by qPCR and ELISA respectively. The signaling pathway-related proteins were investigated by western blot and immunofluorescence assay.
  
  
  RESULTS
  HBcAg increased the expression and secretion of IL-6 through activating extracellular signal-related kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB). These activations can be blocked by specific inhibitors of the three pathways.
  
  
  CONCLUSIONS
  HBcAg actives p38, ERK1/2 and NF-κB to enhance the production of IL-6 in hepatocytes. This provides a molecular mechanism to explain the association of cytoplasmic HBcAg with severe liver injury and inflammation.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Yang-Xia
authors.initials: YX
authors.lastname: Li
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Fu
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Ren
authors.forename: Ling
authors.initials: L
authors.lastname: Zou
authors.forename: Shi-Zhen
authors.initials: SZ
authors.lastname: Shen
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Huang
mesh_terms: D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D006512:Hepatitis B Core Antigens; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
keywords: ERK; Hepatitis B core antigen; IL-6; NF-κB; p38 MAPK