Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 378, Issue 3, Pages 348-353Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.10.155
Keywords
TNF alpha; Tumor necrosis factor alpha; Knockout mice; Bile duct ligation; BDL; Cholestasis; Liver fibrosis; TGF-beta
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Funding
- German Research Association [He 2458/14-1, Fr 1644/4-1, Ga 1272/2-1]
- Medical Faculty of the University of Regensburg (ReForM)
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TNF alpha, a mediator of hepatotoxicity in several animal models, is elevated in acute and chronic liver diseases. Therefore, we investigated whether hepatic injury and fibrosis due to bile duct ligation (BDL) would be reduced in TNF alpha knockout mice (TNF alpha-/-). Survival after BDL was 60% in wild-type mice (TNF alpha+/+) and 90% in TNF alpha-/- mice. Body weight loss and liver to body weight ratios were reduced in TNFa-/- mice compared to TNF alpha+/+ mice. Following BDL, serum alanine transaminases (ALT) levels were elevated in TNF alpha+/+ mice (268.6 +/- 28.2 U/L) compared to TNF alpha-/- mice (105.9 U/L +/- 24.4). TNF alpha-/- mice revealed lower hepatic collagen expression and less liver fibrosis in the histology. Further, alpha-smooth muscle actin, an indicator for activated myofibroblasts, and TGF-beta mRNA, a profibrogenic cytokine, were markedly reduced in TNF alpha-/- mice compared to TNF alpha+/+ mice. Thus, our data indicate that TNF alpha induces hepatotoxicity and promotes fibrogenesis in the BDL model. (C) 2008 Elsevier Inc. All rights reserved.
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