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Article

IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism

1
Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Osaka 598-8531, Japan
2
Molecular Toxicology Laboratory, Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan
3
Laboratory of Veterinary Pathology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Osaka 598-8531, Japan
4
Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan
5
Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Academic Editor: Bernhard Ryffel
Cells 2021, 10(12), 3513; https://doi.org/10.3390/cells10123513
Received: 18 November 2021 / Revised: 2 December 2021 / Accepted: 9 December 2021 / Published: 13 December 2021
(This article belongs to the Special Issue The Increasingly Fascinating World of Interleukins)
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-α, and TGF-β 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. View Full-Text
Keywords: IL-19; NAFLD; NASH; inflammation; liver; lipogenesis IL-19; NAFLD; NASH; inflammation; liver; lipogenesis
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MDPI and ACS Style

Azuma, Y.-T.; Fujita, T.; Izawa, T.; Hirota, K.; Nishiyama, K.; Ikegami, A.; Aoyama, T.; Ike, M.; Ushikai, Y.; Kuwamura, M.; Fujii, H.; Tsuneyama, K. IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism. Cells 2021, 10, 3513. https://doi.org/10.3390/cells10123513

AMA Style

Azuma Y-T, Fujita T, Izawa T, Hirota K, Nishiyama K, Ikegami A, Aoyama T, Ike M, Ushikai Y, Kuwamura M, Fujii H, Tsuneyama K. IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism. Cells. 2021; 10(12):3513. https://doi.org/10.3390/cells10123513

Chicago/Turabian Style

Azuma, Yasu-Taka, Takashi Fujita, Takeshi Izawa, Kana Hirota, Kazuhiro Nishiyama, Airi Ikegami, Tomoko Aoyama, Mikihito Ike, Yumi Ushikai, Mitsuru Kuwamura, Hideki Fujii, and Koichi Tsuneyama. 2021. "IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism" Cells 10, no. 12: 3513. https://doi.org/10.3390/cells10123513

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