Interferon-gamma exacerbates liver damage, the hepatic progenitor cell response and fibrosis in a mouse model of chronic liver injury.
OBJECTIVE
Several previous studies have suggested that interferon gamma (IFNgamma) may play a key role during hepatic progenitor cell (HPC) mediated liver regeneration. However to date, no studies have directly tested the ability of IFNgamma to mediate the HPC response in an in vivo model.


RESULTS
Administration of IFNgamma to mice receiving a choline deficient, ethionine (CDE) supplemented diet to induce chronic injury resulted in an augmented HPC response. This was accompanied by increased inflammation, altered cytokine expression and hepatic fibrosis. Serum alanine aminotransferase activity, hepatocyte apoptosis and Bak staining were significantly increased in IFNgamma-treated, CDE-fed mice, demonstrating that liver damage was exacerbated in these animals. Administration of IFNgamma to control diet fed mice did not induce liver damage, however it did stimulate hepatic inflammation.


CONCLUSIONS
Our results suggest that IFNgamma increases the HPC response to injury by stimulating hepatic inflammation and aggravating liver damage. This is accompanied by an increase in hepatic fibrogenesis, supporting previous reports which suggest that the HPC response may drive fibrogenesis during chronic liver injury.
Knight
Belinda
B
School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital Campus, PO Box 480, Fremantle 6959, WA, Australia.
Lim
Rebecca
R
Yeoh
George C
GC
Olynyk
John K
JK
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D002908:Chronic Disease; D004032:Diet; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000096:biosynthesis; D022781:Hepatocytes / Q000166:cytology; D007249:Inflammation / Q000139:chemically induced; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects*; D008103:Liver Cirrhosis / Q000139:chemically induced*; D051379:Mice; D011994:Recombinant Proteins; D013234:Stem Cells / Q000187:drug effects*
D011994:Recombinant Proteins; D007371:Interferon-gamma; D005340:Fibrinogen