{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:05:04Z","timestamp":1781841904538,"version":"3.54.5"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research (C)","award":["18K05978"],"award-info":[{"award-number":["18K05978"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Interleukin (IL)-19, a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. Nonalcoholic steatohepatitis (NASH) is a disease that has progressed from nonalcoholic fatty liver disease (NAFLD) and is characterized by inflammation and fibrosis. We evaluated the functions of IL-19 in a NAFLD\/NASH mouse model using a 60% high fat diet with 0.1% methionine, without choline, and with 2% cholesterol (CDAHFD). Wild-type (WT) and IL-19 gene-deficient (KO) mice were fed a CDAHFD or standard diet for 9 weeks. Liver injury, inflammation, and fibrosis induced by CDAHFD were significantly worse in IL-19 KO mice than in WT mice. IL-6, TNF-\u03b1, and TGF-\u03b2 were significantly higher in IL-19 KO mice than in WT mice. As a mechanism using an in vitro experiment, palmitate-induced triglyceride and cholesterol contents were decreased by the addition of IL-19 in HepG2 cells. Furthermore, addition of IL-19 decreased the expression of fatty acid synthesis-related enzymes and increased ATP content in HepG2 cells. The action of IL-19 in vitro suppressed lipid metabolism. In conclusion, IL-19 may play an important role in the development of steatosis and fibrosis by directly regulating liver metabolism and may be a potential target for the treatment of liver diseases.<\/jats:p>","DOI":"10.3390\/cells10123513","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T01:20:41Z","timestamp":1639444841000},"page":"3513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3515-171X","authenticated-orcid":false,"given":"Yasu-Taka","family":"Azuma","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7417-3551","authenticated-orcid":false,"given":"Takashi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory, Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3236-6050","authenticated-orcid":false,"given":"Takeshi","family":"Izawa","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Hirota","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-3562","authenticated-orcid":false,"given":"Kazuhiro","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Airi","family":"Ikegami","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory, Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory, Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikihito","family":"Ike","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory, Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Ushikai","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Kuwamura","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Osaka 598-8531, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Tsuneyama","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.2174\/138161211798357845","article-title":"IL-19 as a potential therapeutic in autoimmune and inflammatory diseases","volume":"17","author":"Azuma","year":"2011","journal-title":"Curr. 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