| Autor: |
Reifenberg, Kurt, Hildt, Eberhard, Lecher, Bernd, Wiese, Elena, Nusser, Petra, Ott, Sibylle, Yamamura, Ken-Ichi, Rutter, Gabriel, Löhler, Jürgen |
| Předmět: |
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| Zdroj: |
Liver International; Oct2006, Vol. 26 Issue 8, p986-993, 8p, 3 Diagrams, 1 Graph |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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