抄録
Background: IL-19 is a member of the IL-10 family and is an anti-inflammatory cytokine produced by the main macrophages. Nonalcoholic fatty liver disease (NAFLD) is highly associated with the metabolic syndrome, and occurs as a more serious form of the disease, nonalcoholic steatohepatitis (NASH). NASH is diagnosed pathologically by histological evaluation of fibrosis, inflammation, and other features, such as hepatocyte ballooning. However, the involvement of IL-19 in liver inflammation and liver fibrosis is not well understood. We investigated the immunological role of IL-19 in diet-induced NAFLD/NASH model mice.
Methods: C57BL/6 genetic background IL-19 knockout (KO) mice and age-matched wild-type (WT) mice were fed a choline-deficient and high-fat diet (60kcal% fat) with 0.1% methionine and 2% cholesterol (CDAHFD) for 2 months. Histological evaluation in the liver was assessed by HE staining, Azan staining, and CD68 immunohistochemistry. mRNA expression in the liver was analyzed quantitative real-time PCR.
Result: IL-19 KO mice showed significantly weight loss on 2 months compared with WT mice. Liver weight on 2 months was significantly less in IL-19 KO than WT mice. Histological analyses of the liver from WT mice showed moderate steatosis, mild inflammation, and no fibrosis, indicating that WT mice have steatohepatitis. IL-19 KO mice showed significantly high ALT level compared with WT mice. Moreover, IL-19KO mice showed weaker steatosis and more severe inflammation than WT mice. Specifically, IL-19 KO mice showed pericellular fibrosis that is one of the features of NASH. Additionally, mRNA expression levels of TNF-alpha and IL-6 were significantly increased in IL-19 KO mice compared with WT mice.
Conclusion: Our findings indicate that IL-19 has previously undocumented roles in the progress of fibrosis and the elimination of inflammation in the liver. IL-19 KO mice may be a valuable tool to study the NAFLD/NASH mice model.
