IFNγ expression inhibits LHBs storage disease and ground glass hepatocyte appearance, but exacerbates inflammation and apoptosis in HBV surface protein-accumulating transgenic livers
Article first published online: 10 AUG 2006
Volume 26, Issue 8, pages 986–993, October 2006
How to Cite
Reifenberg, K., Hildt, E., Lecher, B., Wiese, E., Nusser, P., Ott, S., Yamamura, K.-I., Rutter, G. and Löhler, J. (2006), IFNγ expression inhibits LHBs storage disease and ground glass hepatocyte appearance, but exacerbates inflammation and apoptosis in HBV surface protein-accumulating transgenic livers. Liver International, 26: 986–993. doi: 10.1111/j.1478-3231.2006.01317.x
- Issue published online: 5 SEP 2006
- Article first published online: 10 AUG 2006
- Received 4 April 2006,accepted 22 May 2006
- chronic hepatitis B;
- ground glass hepatocyte;
- hepatitis B virus;
- LHBs storage;
- transgenic mice
Abstract: Background/Aims: Interferon γ (IFNγ) controls hepatitis B virus replication. As systemic application may cause severe adverse effects, approaches of liver-directed IFNγ gene therapy may represent an attractive alternative for treatment of chronic viral hepatitis B and thus needs testing in vivo in suitable animal models.
Methods: We therefore crossbred Alb-1HBV transgenic mice overexpressing the large HBV surface protein (LHBs) in their livers and developing LHBs storage disease and ground glass hepatocyte appearance with SAP-IFNγ transgenic animals previously shown to exhibit constitutive hepatic IFNγ expression, and analyzed the resulting double-transgenic offspring.
Results: We found that IFNγ coexpression significantly reduced hepatic LHBs expression and thereby inhibited hepatocellular LHBs storage disease and ground glass hepatocyte appearance. The beneficial antiviral IFNγ effects as observed in Alb1-HBV SAP-IFNγ double-transgenic livers were associated with significantly elevated serum ALT concentrations, massive mononuclear cell infiltrates, appearance of Councilman bodies, and increased α-PARP (poly(ADP-ribose) polymerase cleavage).
Conclusions: Exacerbation of hepatic necroinflammation and increased hepatocellular apoptosis rate in IFNγ-expressing Alb1-HBV transgenic livers suggest that special precautions be taken for testing approaches of liver-specific IFNγ expression in patients with chronic hepatitis B.