Premium
IFNγ expression inhibits LHBs storage disease and ground glass hepatocyte appearance, but exacerbates inflammation and apoptosis in HBV surface protein‐accumulating transgenic livers
Author(s) -
Reifenberg Kurt,
Hildt Eberhard,
Lecher Bernd,
Wiese Elena,
Nusser Petra,
Ott Sibylle,
Yamamura KenIchi,
Rutter Gabriel,
Löhler Jürgen
Publication year - 2006
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2006.01317.x
Subject(s) - hepatocellular carcinoma , hepatocyte , hepatitis b virus , apoptosis , transgene , liver disease , genetically modified mouse , peripheral blood mononuclear cell , interferon , in vivo , inflammation , cancer research , immunology , medicine , biology , virology , virus , in vitro , gene , microbiology and biotechnology , biochemistry
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.