| First Author | Reifenberg K | Year | 2006 |
| Journal | Liver Int | Volume | 26 |
| Issue | 8 | Pages | 986-93 |
| PubMed ID | 16953839 | Mgi Jnum | J:135035 |
| Mgi Id | MGI:3790276 | Doi | 10.1111/j.1478-3231.2006.01317.x |
| Citation | Reifenberg K, et al. (2006) IFNgamma expression inhibits LHBs storage disease and ground glass hepatocyte appearance, but exacerbates inflammation and apoptosis in HBV surface protein-accumulating transgenic livers. Liver Int 26(8):986-93 |
| abstractText | BACKGROUND/AIMS: Interferon gamma (IFNgamma) controls hepatitis B virus replication. As systemic application may cause severe adverse effects, approaches of liver-directed IFNgamma 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-IFNgamma transgenic animals previously shown to exhibit constitutive hepatic IFNgamma expression, and analyzed the resulting double-transgenic offspring. RESULTS: We found that IFNgamma coexpression significantly reduced hepatic LHBs expression and thereby inhibited hepatocellular LHBs storage disease and ground glass hepatocyte appearance. The beneficial antiviral IFNgamma effects as observed in Alb1-HBV SAP-IFNgamma double-transgenic livers were associated with significantly elevated serum ALT concentrations, massive mononuclear cell infiltrates, appearance of Councilman bodies, and increased alpha-PARP (poly(ADP-ribose) polymerase cleavage). CONCLUSIONS: Exacerbation of hepatic necroinflammation and increased hepatocellular apoptosis rate in IFNgamma-expressing Alb1-HBV transgenic livers suggest that special precautions be taken for testing approaches of liver-specific IFNgamma expression in patients with chronic hepatitis B. |
