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Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-β Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis

IL-19 is a cytokine discovered by homologous searching with IL-10 and is produced by non-immune cells, such as keratinocytes, in addition to immune cells, such as macrophages. Liver fibrosis results from the inflammation and activation of hepatic stellate cells via chronic liver injury. However, the...

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Autores principales: Ono, Naoshige, Fujita, Takashi, Miki, Mariko, Nishiyama, Kazuhiro, Izawa, Takeshi, Aoyama, Tomoko, Kuwamura, Mitsuru, Fujii, Hideki, Azuma, Yasu-Taka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377488/
https://www.ncbi.nlm.nih.gov/pubmed/37509702
http://dx.doi.org/10.3390/biomedicines11072064
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author Ono, Naoshige
Fujita, Takashi
Miki, Mariko
Nishiyama, Kazuhiro
Izawa, Takeshi
Aoyama, Tomoko
Kuwamura, Mitsuru
Fujii, Hideki
Azuma, Yasu-Taka
author_facet Ono, Naoshige
Fujita, Takashi
Miki, Mariko
Nishiyama, Kazuhiro
Izawa, Takeshi
Aoyama, Tomoko
Kuwamura, Mitsuru
Fujii, Hideki
Azuma, Yasu-Taka
author_sort Ono, Naoshige
collection PubMed
description IL-19 is a cytokine discovered by homologous searching with IL-10 and is produced by non-immune cells, such as keratinocytes, in addition to immune cells, such as macrophages. Liver fibrosis results from the inflammation and activation of hepatic stellate cells via chronic liver injury. However, the participation of IL-19 in liver fibrosis remains to be sufficiently elucidated. Our group studied the immunological function of IL-19 in a mouse model of carbon tetrachloride (CCl(4))-induced liver fibrosis. IL-19 gene-deficient (KO) mice and body weight-matched wild-type (WT) mice were used. A liver fibrosis mouse model was created via CCl(4) administration (two times per week) for 8 weeks. In CCl(4)-induced liver fibrosis, serum analysis revealed that IL-19 KO mice had higher ALT levels compared to WT mice. IL-19 KO mice had worse fibrosis, as assessed by morphological evaluation of total area stained positive with Azan and Masson trichrome. In addition, the expression of α-SMA was increased in liver tissues of IL-19 KO mice compared to WT mice. Furthermore, mRNA expression levels of TGF-β and α-SMA were enhanced in IL-19 KO mice compared to WT mice. In vitro assays revealed that IL-19-high expressing RAW264.7 cells inhibited the migration of NIH3T3 cells via the inhibited expression of CCL2 in the presence of CCl(4) and IL-4. These findings indicate that IL-19 plays a critical role in liver fibrosis by affecting TGF-β signaling and the migration of hepatic stellate cells during liver injury. Enhancement of the IL-19 signaling pathway is a potential treatment for liver fibrosis.
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spelling pubmed-103774882023-07-29 Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-β Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis Ono, Naoshige Fujita, Takashi Miki, Mariko Nishiyama, Kazuhiro Izawa, Takeshi Aoyama, Tomoko Kuwamura, Mitsuru Fujii, Hideki Azuma, Yasu-Taka Biomedicines Article IL-19 is a cytokine discovered by homologous searching with IL-10 and is produced by non-immune cells, such as keratinocytes, in addition to immune cells, such as macrophages. Liver fibrosis results from the inflammation and activation of hepatic stellate cells via chronic liver injury. However, the participation of IL-19 in liver fibrosis remains to be sufficiently elucidated. Our group studied the immunological function of IL-19 in a mouse model of carbon tetrachloride (CCl(4))-induced liver fibrosis. IL-19 gene-deficient (KO) mice and body weight-matched wild-type (WT) mice were used. A liver fibrosis mouse model was created via CCl(4) administration (two times per week) for 8 weeks. In CCl(4)-induced liver fibrosis, serum analysis revealed that IL-19 KO mice had higher ALT levels compared to WT mice. IL-19 KO mice had worse fibrosis, as assessed by morphological evaluation of total area stained positive with Azan and Masson trichrome. In addition, the expression of α-SMA was increased in liver tissues of IL-19 KO mice compared to WT mice. Furthermore, mRNA expression levels of TGF-β and α-SMA were enhanced in IL-19 KO mice compared to WT mice. In vitro assays revealed that IL-19-high expressing RAW264.7 cells inhibited the migration of NIH3T3 cells via the inhibited expression of CCL2 in the presence of CCl(4) and IL-4. These findings indicate that IL-19 plays a critical role in liver fibrosis by affecting TGF-β signaling and the migration of hepatic stellate cells during liver injury. Enhancement of the IL-19 signaling pathway is a potential treatment for liver fibrosis. MDPI 2023-07-22 /pmc/articles/PMC10377488/ /pubmed/37509702 http://dx.doi.org/10.3390/biomedicines11072064 Text en © 2023 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
Ono, Naoshige
Fujita, Takashi
Miki, Mariko
Nishiyama, Kazuhiro
Izawa, Takeshi
Aoyama, Tomoko
Kuwamura, Mitsuru
Fujii, Hideki
Azuma, Yasu-Taka
Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-β Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis
title Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-β Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis
title_full Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-β Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis
title_fullStr Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-β Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis
title_full_unstemmed Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-β Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis
title_short Interleukin-19 Gene-Deficient Mice Promote Liver Fibrosis via Enhanced TGF-β Signaling, and the Interleukin-19-CCL2 Axis Is Important in the Direction of Liver Fibrosis
title_sort interleukin-19 gene-deficient mice promote liver fibrosis via enhanced tgf-β signaling, and the interleukin-19-ccl2 axis is important in the direction of liver fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377488/
https://www.ncbi.nlm.nih.gov/pubmed/37509702
http://dx.doi.org/10.3390/biomedicines11072064
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