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

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 th...

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Autores principales: Azuma, Yasu-Taka, Fujita, Takashi, Izawa, Takeshi, Hirota, Kana, Nishiyama, Kazuhiro, Ikegami, Airi, Aoyama, Tomoko, Ike, Mikihito, Ushikai, Yumi, Kuwamura, Mitsuru, Fujii, Hideki, Tsuneyama, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699936/
https://www.ncbi.nlm.nih.gov/pubmed/34944021
http://dx.doi.org/10.3390/cells10123513
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author Azuma, Yasu-Taka
Fujita, Takashi
Izawa, Takeshi
Hirota, Kana
Nishiyama, Kazuhiro
Ikegami, Airi
Aoyama, Tomoko
Ike, Mikihito
Ushikai, Yumi
Kuwamura, Mitsuru
Fujii, Hideki
Tsuneyama, Koichi
author_facet Azuma, Yasu-Taka
Fujita, Takashi
Izawa, Takeshi
Hirota, Kana
Nishiyama, Kazuhiro
Ikegami, Airi
Aoyama, Tomoko
Ike, Mikihito
Ushikai, Yumi
Kuwamura, Mitsuru
Fujii, Hideki
Tsuneyama, Koichi
author_sort Azuma, Yasu-Taka
collection PubMed
description 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.
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spelling pubmed-86999362021-12-24 IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism Azuma, Yasu-Taka Fujita, Takashi Izawa, Takeshi Hirota, Kana Nishiyama, Kazuhiro Ikegami, Airi Aoyama, Tomoko Ike, Mikihito Ushikai, Yumi Kuwamura, Mitsuru Fujii, Hideki Tsuneyama, Koichi Cells Article 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. MDPI 2021-12-13 /pmc/articles/PMC8699936/ /pubmed/34944021 http://dx.doi.org/10.3390/cells10123513 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Azuma, Yasu-Taka
Fujita, Takashi
Izawa, Takeshi
Hirota, Kana
Nishiyama, Kazuhiro
Ikegami, Airi
Aoyama, Tomoko
Ike, Mikihito
Ushikai, Yumi
Kuwamura, Mitsuru
Fujii, Hideki
Tsuneyama, Koichi
IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism
title IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism
title_full IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism
title_fullStr IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism
title_full_unstemmed IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism
title_short IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism
title_sort il-19 contributes to the development of nonalcoholic steatohepatitis by altering lipid metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699936/
https://www.ncbi.nlm.nih.gov/pubmed/34944021
http://dx.doi.org/10.3390/cells10123513
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