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Prevention of hepatic fibrosis in nonobese diabetic mice: a critical role for interferon‐γ
Author(s) -
Mukai Tsuyoshi,
Nagaki Masahito,
Imose Motoaki,
Kimura Kiminori,
Satake Shinichi,
Takai Shinji,
Moriwaki Hisataka
Publication year - 2006
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2006.01322.x
Subject(s) - nod , nod mice , cirrhosis , hepatic fibrosis , medicine , fibrosis , interferon gamma , liver injury , hepatic stellate cell , intraperitoneal injection , immune system , cytokine , interferon , endocrinology , immunology , diabetes mellitus
Background/Aims: Nonobese diabetic (NOD) mice, a model of type I diabetes mellitus, harbor certain unique defects in their immune system. The aim of this study was to investigate how NOD mice show hepatic injury and subsequent fibrogenic responses. Methods: Hepatic fibrosis was induced by intraperitoneal injections of dimethylnitrosamine (DMN), and assessed biochemically and histologically. Expressions of cytokine messenger RNA (mRNA) in the liver were determined. Results: In a model of liver cirrhosis induced by dimethylnitrosamine (DMN), we found that NOD mice had lower levels of hepatic fibrosis and better survival than control ICR mice. The resistance to DMN‐induced lethality in NOD mice was independent of apoptosis and necrosis of hepatocytes, but apparently due to the prevention of hepatic fibrosis. We also found increased inductions of interferon‐γ (IFN‐γ) mRNA in the liver of NOD mice and of intracellular IFN‐γ from intrahepatic T cells following DMN administration. Treatment with neutralizing anti‐IFN‐γ‐antibody cancelled the inhibition of hepatic fibrosis in NOD mice. Conclusions: These results suggest that IFN‐γ is effective for inhibiting hepatic fibrosis and that genetic host factors may be important in determining differential responses to injury.