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In a steatohepatitis model by feeding a methionine- and choline-deficient high-fat (MCDHF) diet to both wild-type and IFN-\u03b3-deficient mice, the liver histology, expression of genes encoding inflammatory cytokines, and fibrosis-related markers were examined. To analyze the effects of IFN-\u03b3 on Kupffer cells in vitro, we examined the tumor necrosis factor-\u03b1 (TNF-\u03b1) production by a mouse macrophage cell line. Forty two days of MCDHF diet resulted in weight loss, elevated aminotransferases, liver steatosis, and inflammation in wild-type mice. However, the IFN-\u03b3-deficient mice exhibited less extensive changes. RT-PCR revealed that the expression of tumor necrosis factor-\u03b1 (TNF-\u03b1), transforming growth factor-\u03b2, inducible nitric oxide synthase, interleukin-4 and osteopontin were increased in wild-type mice, although they were suppressed in IFN-\u03b3-deficient mice. Seventy days of MCDHF diet induced much more liver fibrosis in wild-type mice than in IFN-\u03b3-deficient mice. The expression levels of fibrosis-related genes, \u03b1-smooth muscle actin, type I collagen, tissue inhibitor of matrix metalloproteinase-1, and matrix metalloproteinase-2, were dramatically increased in wild-type mice, whereas they were significantly suppressed in IFN-\u03b3-deficient mice. Moreover, in vitro experiments showed that, when RAW 264.7 macrophages were treated with IFN-\u03b3, they produced TNF-\u03b1 in a dose-dependent manner. The present study showed that IFN-\u03b3 deficiency might inhibit the inflammatory response of macrophages cells and subsequently suppress stellate cell activation and liver fibrosis. These findings highlight the critical role of IFN-\u03b3 in the progression of steatohepatitis.<\/jats:p>","DOI":"10.1152\/ajpgi.00193.2013","type":"journal-article","created":{"date-parts":[[2013,10,18]],"date-time":"2013-10-18T03:33:17Z","timestamp":1382067197000},"page":"G891-G899","source":"Crossref","is-referenced-by-count":113,"title":["IFN-\u03b3 deficiency attenuates hepatic inflammation and fibrosis in a steatohepatitis model induced by a methionine- and choline-deficient high-fat diet"],"prefix":"10.1152","volume":"305","author":[{"given":"Xiao-Yu","family":"Luo","sequence":"first","affiliation":[{"name":"Division for Transplantation Immunology, National Institute for Child Health and Development, Tokyo, Japan;"},{"name":"Second Department of Surgery, University of Toyama, Toyama, Japan;"},{"name":"Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, 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