MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function

Acute liver injury (ALI) raises high mortality rates due to a rapid pathological process. MCC950, a highly selective nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor, has already been reported to show strong hepatoprotective effects in many different liver diseases. In this study...

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Autores principales:	Wei Yan, Yingchun Shen, Jinny Huang, Ling Lu, Qian Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	MCC950 acute liver injury macrophage polarization myeloid-derived suppressor cells treatment Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3fd6ab646b794c8082d4b3fd2ab6caef
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spelling	oai:doaj.org-article:3fd6ab646b794c8082d4b3fd2ab6caef2021-11-19T06:33:13ZMCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function2296-858X10.3389/fmed.2021.752223https://doaj.org/article/3fd6ab646b794c8082d4b3fd2ab6caef2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.752223/fullhttps://doaj.org/toc/2296-858XAcute liver injury (ALI) raises high mortality rates due to a rapid pathological process. MCC950, a highly selective nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor, has already been reported to show strong hepatoprotective effects in many different liver diseases. In this study, we unveiled the role of MCC950 in carbon tetrachloride (CCl4)-induced ALI and its underlying molecular mechanisms on days 1, 2, and 3. MCC950 could significantly inhibit liver injury, evidenced by decreased serum alamine aminotransferase (ALT) and aspartate aminotransferase (AST) levels on days 1 and 2, increased Albumin (ALB) level on day 3, and decreased histological score during the whole period. Moreover, lower M1 macrophage related to pro-inflammatory genes expression was observed in MCC950-treated ALI mice on day 1, while MCC950 pretreatment also polarized macrophage to M2 phenotype indicating anti-inflammatory response on days 2 and 3. Additionally, MDSC was significantly increased in blood, liver, and spleen in ALI mice at different time courses. Specifically, upregulated myeloid-derived suppressor cell (MDSC) proportions were found in blood and spleen on days 1 and 2, but showed decreased trend on day 3. However, liver MDSC numbers were increased on days 2 and 3, but no significance on day 1. In conclusion, MCC950 pretreatment alleviates CCl4-induced ALI through enhanced M2 macrophage and MDSC function at different time points of ALI. Further understanding of MCC950 in ALI may be a new potential therapeutic strategy.Wei YanWei YanYingchun ShenJinny HuangLing LuQian ZhangFrontiers Media S.A.articleMCC950acute liver injurymacrophage polarizationmyeloid-derived suppressor cellstreatmentMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MCC950 acute liver injury macrophage polarization myeloid-derived suppressor cells treatment Medicine (General) R5-920
spellingShingle	MCC950 acute liver injury macrophage polarization myeloid-derived suppressor cells treatment Medicine (General) R5-920 Wei Yan Wei Yan Yingchun Shen Jinny Huang Ling Lu Qian Zhang MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function
description	Acute liver injury (ALI) raises high mortality rates due to a rapid pathological process. MCC950, a highly selective nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor, has already been reported to show strong hepatoprotective effects in many different liver diseases. In this study, we unveiled the role of MCC950 in carbon tetrachloride (CCl4)-induced ALI and its underlying molecular mechanisms on days 1, 2, and 3. MCC950 could significantly inhibit liver injury, evidenced by decreased serum alamine aminotransferase (ALT) and aspartate aminotransferase (AST) levels on days 1 and 2, increased Albumin (ALB) level on day 3, and decreased histological score during the whole period. Moreover, lower M1 macrophage related to pro-inflammatory genes expression was observed in MCC950-treated ALI mice on day 1, while MCC950 pretreatment also polarized macrophage to M2 phenotype indicating anti-inflammatory response on days 2 and 3. Additionally, MDSC was significantly increased in blood, liver, and spleen in ALI mice at different time courses. Specifically, upregulated myeloid-derived suppressor cell (MDSC) proportions were found in blood and spleen on days 1 and 2, but showed decreased trend on day 3. However, liver MDSC numbers were increased on days 2 and 3, but no significance on day 1. In conclusion, MCC950 pretreatment alleviates CCl4-induced ALI through enhanced M2 macrophage and MDSC function at different time points of ALI. Further understanding of MCC950 in ALI may be a new potential therapeutic strategy.
format	article
author	Wei Yan Wei Yan Yingchun Shen Jinny Huang Ling Lu Qian Zhang
author_facet	Wei Yan Wei Yan Yingchun Shen Jinny Huang Ling Lu Qian Zhang
author_sort	Wei Yan
title	MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function
title_short	MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function
title_full	MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function
title_fullStr	MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function
title_full_unstemmed	MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function
title_sort	mcc950 ameliorates acute liver injury through modulating macrophage polarization and myeloid-derived suppressor cells function
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3fd6ab646b794c8082d4b3fd2ab6caef
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MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells Function

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