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

Mi Ock Lee, Youn Hee Choi, Eui Cheol Shin, Hyo Jin Kang, Young Mee Kim, Su Yon Jeong, Je Kyung Seong, Dae Yeul Yu, Hyeseong Cho, Jeon Han Park, Se Jong Kim

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62 Scopus citations


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.

Original languageEnglish
Pages (from-to)380-386
Number of pages7
JournalJournal of Hepatology
Issue number3
StatePublished - Sep 2002

Bibliographical note

Funding Information:
We thank Dr H. Tsutsi (Hyogo College of Medicine, Hyogo, Japan) for providing the IL-18-responsive LNK5E3 cells. This study was supported by a grant of the 2000 Good Health R&D Project (HMP-00-B-21200-0043 to M.O.L) from the Ministry of Health and Welfare, Korea.


  • Fas ligand
  • Hepatitis B virus X protein
  • Interleukin 18
  • Liver injury


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