Interferon gamma treatment prevents procollagen gene expression without affecting transforming growth factor-beta1 expression in pig serum-induced rat liver fibrosis in vivo.
OBJECTIVE
The aim of this study was to investigate the effect of interferon gamma on the synthesis of matrix proteins such as collagens with the relation to transforming growth factor-beta1 expression in vivo.


METHODS
We investigated the effects of interferon gamma in a model of liver fibrosis induced by pig serum in male Wistar rats, which develops fibrosis without an increase in serum alanine aminotransferase (i.e., without hepatocyte injury). Rats were injected with 0.5 ml of pig serum twice a week for 8 weeks with or without 20,000 or 50,000 U of interferon gamma.


RESULTS
Interferon gamma at doses up to 50,000 U/day prevented fibrosis, as indicated by reduced hydroxyproline content in the liver. Interferon gamma at 50,000 U/day also reduced expression of type I and III procollagen in the liver. However, the expression of transforming growth factor-beta1 mRNA and protein in the liver was not reduced by interferon gamma. Histologically, interferon gamma at 50,000 U/day also reduced the number of myofibroblast-like cells (activated stellate cells).


CONCLUSIONS
These results indicate that interferon gamma can prevent fibrosis by inhibiting the activation and proliferation of stellate cells, resulting in reduced expression of procollagen without affecting transforming growth factor-beta1 expression in pig serum-induced rat liver fibrosis in vivo.
Sakaida
I
I
First Department of Internal Medicine, School of Medicine, Yamaguchi University, Ube, Japan.
Uchida
K
K
Matsumura
Y
Y
Okita
K
K
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D006909:Hydroxyproline / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D011347:Procollagen / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine / Q000097:blood; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D000998:Antiviral Agents; D015415:Biomarkers; D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D006909:Hydroxyproline