Interferon-alpha Response in Chronic Hepatitis B-transfected HepG2.2.15 Cells is Partially Restored by Lamivudine Treatment

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2007 Jan 18

PMID 17226901

Citations 11

Authors

Shi-He Guan

Mengji Lu

Petra Grunewald

Michael Roggendorf

Guido Gerken

Jorg F Schlaak

Affiliations

Soon will be listed here.

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-alpha2a 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-alpha 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-alpha 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.

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