Interferon-α responce in chronic hepatitis B-transfected HepG2.2.15 cells is partially restored by lamivudine treatment

Shi He Guan, Mengji Lu, Petra Grünewald, Michael Roggendorf, Guido Gerken, Jörg F. Schlaak

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Aim: To characterize the IFN-response and its modulation by the antiviral compound lamivudine in HBV-transfected HepG2.2.15 cells. Methods: HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-α2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes (ISGs). In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. Results: Two genes (MxA, Cig5) with completely abolished and 4 genes (IFITM1, -2, -3, and 6-16) with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes (IFITM1, 6-16), the response to IFN-α could be restored by treatment with lamivudine, This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Stat1 activation and ISGF3 formation after stimulation with IFN-α in HepG2.2.15 compared to HepG2 cells. Conclusion: These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expression by reducing HBV gene expression and replication.

Original languageEnglish
Pages (from-to)228-235
Number of pages8
JournalWorld Journal of Gastroenterology
Volume13
Issue number2
DOIs
StatePublished - 14 Jan 2007
Externally publishedYes

Keywords

  • Gene expression
  • Hepatitis B
  • IFN-α
  • Lamivudine

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