IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis
Summary: Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear....
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223016218 |
| _version_ | 1797742574088224768 |
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| author | Mengmeng Zhao Zihui Zheng Pingan Zhang Yao Xu Jishou Zhang Shanshan Peng Jianfang Liu Wei Pan Zheng Yin Shuwan Xu Cheng Wei Jun Wan Menglong Wang |
| author_facet | Mengmeng Zhao Zihui Zheng Pingan Zhang Yao Xu Jishou Zhang Shanshan Peng Jianfang Liu Wei Pan Zheng Yin Shuwan Xu Cheng Wei Jun Wan Menglong Wang |
| author_sort | Mengmeng Zhao |
| collection | DOAJ |
| description | Summary: Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear. Here, we explored the protective role of IL-30 in cecum ligation and puncture (CLP)-induced SIMD mice. IL-30 expression increased in the cardiac tissues of septic mice and was mainly derived from macrophages. IL-30 deletion or neutralization aggravated sepsis-induced cardiac dysfunction and injury, whereas recombinant IL-30 treatment significantly ameliorated it. Mechanistically, IL-30 deficiency exerts pro-inflammatory effects by promoting Ly6Chigh macrophage polarization and pyroptosis. Inhibiting NLRP3 with MCC950 significantly reversed cardiac dysfunction, macrophage polarization and pyroptosis aggravated by IL-30 deficiency. Recombinant IL-30 inhibited pro-inflammatory macrophage polarization and pyroptosis in vivo and vitro. Taken together, these results suggest that IL-30 protects against SIMD by inhibiting pro-inflammatory macrophage polarization and pyroptosis. |
| first_indexed | 2024-03-12T14:42:38Z |
| format | Article |
| id | doaj.art-0def4e4619474f4495cec5bb5c8c1417 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T14:42:38Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-0def4e4619474f4495cec5bb5c8c14172023-08-16T04:27:11ZengElsevieriScience2589-00422023-09-01269107544IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosisMengmeng Zhao0Zihui Zheng1Pingan Zhang2Yao Xu3Jishou Zhang4Shanshan Peng5Jianfang Liu6Wei Pan7Zheng Yin8Shuwan Xu9Cheng Wei10Jun Wan11Menglong Wang12Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China; Corresponding authorDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, P.R. China; Hubei Key Laboratory of Cardiology, Wuhan 430060, P.R. China; Corresponding authorSummary: Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear. Here, we explored the protective role of IL-30 in cecum ligation and puncture (CLP)-induced SIMD mice. IL-30 expression increased in the cardiac tissues of septic mice and was mainly derived from macrophages. IL-30 deletion or neutralization aggravated sepsis-induced cardiac dysfunction and injury, whereas recombinant IL-30 treatment significantly ameliorated it. Mechanistically, IL-30 deficiency exerts pro-inflammatory effects by promoting Ly6Chigh macrophage polarization and pyroptosis. Inhibiting NLRP3 with MCC950 significantly reversed cardiac dysfunction, macrophage polarization and pyroptosis aggravated by IL-30 deficiency. Recombinant IL-30 inhibited pro-inflammatory macrophage polarization and pyroptosis in vivo and vitro. Taken together, these results suggest that IL-30 protects against SIMD by inhibiting pro-inflammatory macrophage polarization and pyroptosis.http://www.sciencedirect.com/science/article/pii/S2589004223016218Molecular biologyImmunologyImmune responseCell biology |
| spellingShingle | Mengmeng Zhao Zihui Zheng Pingan Zhang Yao Xu Jishou Zhang Shanshan Peng Jianfang Liu Wei Pan Zheng Yin Shuwan Xu Cheng Wei Jun Wan Menglong Wang IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis iScience Molecular biology Immunology Immune response Cell biology |
| title | IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis |
| title_full | IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis |
| title_fullStr | IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis |
| title_full_unstemmed | IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis |
| title_short | IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis |
| title_sort | il 30 protects against sepsis induced myocardial dysfunction by inhibiting pro inflammatory macrophage polarization and pyroptosis |
| topic | Molecular biology Immunology Immune response Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223016218 |
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