title: Hepatitis B virus X protein induced expression of interleukin 18 (IL-18): a potential mechanism for liver injury caused by hepatitis B virus (HBV) infection.
abstract: OBJECTIVE
  The hepatitis B virus X protein (HBx), a major viral transactivator, is implicated in hepatic inflammation, since it induces many pro-inflammatory cytokines at transcriptional level. The aim of this study was to investigate role of HBx in expression of interleukin 18 (IL-18), a newly identified cytokine that up-regulates Fas ligand (FasL) expression.
  
  
  METHODS
  Chang X-34 that expressing HBx under the control of a doxycycline-inducible promoter, and hepatitis B virus (HBV)-integrated hepatoma cell lines were examined for IL-18 expression by Northern and Western blotting analysis. To test the role of IL-18 produced by hepatoma cells, FasL expression was examined by flow cytometry after treatment with neutralizing anti-IL-18 antibodies. Further, IL-18 expression was examined in the liver tissues of HBx-transgenic mice.
  
  
  RESULTS
  Induction of IL-18 following HBx expression in Chang X-34 and the pattern of IL-18 expression in HBV-integrated cell lines, implicated that HBx transcriptionally induces IL-18 expression. Neutralizing anti-IL-18 antibodies blocked the expression of FasL, suggesting that IL-18 plays a critical role in FasL expression. Further, IL-18 expression in the HBx-transgenic liver, was correlated with the degree of hepatitis.
  
  
  CONCLUSIONS
  Our results demonstrated that HBx induces IL-18 expression in liver, which may be associated with hepatic injury by amplifying FasL expression during HBV infection.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Kwangjin-gu, Seoul 140-747, South Korea. molee@sejong.ac.kr
authors.forename: Mi-Ock
authors.initials: MO
authors.lastname: Lee
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Young-Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: Su-Yon
authors.initials: SY
authors.lastname: Jeong
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.forename: Hyeseong
authors.initials: H
authors.lastname: Cho
authors.forename: Jeon Han
authors.initials: JH
authors.lastname: Park
authors.forename: Se Jong
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular; D053222:Fas Ligand Protein; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein