Liver Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 14, 2007; 13(2): 228-235
Published online Jan 14, 2007. doi: 10.3748/wjg.v13.i2.228
Interferon-α response 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
Shi-He Guan, Petra Grünewald, Guido Gerken, Jörg F Schlaak, Department of Gastroenterology and Hepatology, University Hospital of Essen, Essen, Germany
Shi-He Guan, Mengji Lu, Michael Roggendorf, Institute of Virology, University Hospital of Essen, Essen, Germany
Shi-He Guan, Department of Laboratory Medicine, the first Affiliated Hospital of Anhui Medical University, China
Author contributions: All authors contributed equally to the work.
Supported by grants from the Deutsche Forschungsgemeinschaft (DFG SCHL 377/2-2, LU 669/2-1 and GRK 1045/1)
Correspondence to: Jörg F Schlaak, MD, Professor of Medicine, Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, Essen 45122,Germany. joerg.schlaak@uni-essen.de
Telephone: +49-201-7232518 Fax: +49-201-7235749
Received: August 8, 2006
Revised: August 25, 2006
Accepted: September 20, 2006
Published online: January 14, 2007
Abstract

AIM: To characterize the IFN-response and its modul-ation 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.

Keywords: Hepatitis B; IFN-α; Gene expression; Lamivudine