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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.

Lee, MO; Choi, YH; Shin, EC; Kang, HJ; Kim, YM; Jeong, SY; Seong, JK; Yu, DY; Cho, H; Park, JH; Kim, SJ
Journal of hepatology, 37(3):380-386, 2002
Journal Title
Journal of hepatology
BACKGROUND/AIMS: 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.
MeSH terms
AnimalsCarcinoma, HepatocellularFas Ligand ProteinGene Expression Regulation, ViralHepatitis B virus/*physiologyHepatitis B, Chronic/*immunology/pathology/*virologyHepatocytes/immunology/pathology/virologyHumansInterleukin-18/*genetics/secretionLiver/immunology/pathology/virologyLiver NeoplasmsMembrane Glycoproteins/geneticsMiceMice, TransgenicTrans-Activators/*geneticsTranscription, Genetic/physiologyTumor Cells, Cultured
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Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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