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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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.752223/full |
| _version_ | 1818402065612800000 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T08:02:26Z |
| format | Article |
| id | doaj.art-3fd6ab646b794c8082d4b3fd2ab6caef |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-14T08:02:26Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-3fd6ab646b794c8082d4b3fd2ab6caef2022-12-21T23:10:19ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-11-01810.3389/fmed.2021.752223752223MCC950 Ameliorates Acute Liver Injury Through Modulating Macrophage Polarization and Myeloid-Derived Suppressor Cells FunctionWei Yan0Wei Yan1Yingchun Shen2Jinny Huang3Ling Lu4Qian Zhang5Hepatobiliary Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDivision of Allergy and Clinical Immunology, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesHepatobiliary Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaAcute 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.https://www.frontiersin.org/articles/10.3389/fmed.2021.752223/fullMCC950acute liver injurymacrophage polarizationmyeloid-derived suppressor cellstreatment |
| spellingShingle | 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 Frontiers in Medicine MCC950 acute liver injury macrophage polarization myeloid-derived suppressor cells treatment |
| title | 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_short | 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 |
| topic | MCC950 acute liver injury macrophage polarization myeloid-derived suppressor cells treatment |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.752223/full |
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