Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis
Abstract Myocardial ischemia reperfusion (I/R) injury is a complex process with intense inflammatory response and cardiomyocyte apoptosis. As a decoy receptor of IL-1β, Interleukin-1 receptor type 2 (IL-1R2) inhibits IL-1β signaling. However, its role in I/R injury remains unknown. Here we found tha...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04533-1 |
| _version_ | 1819349858916499456 |
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| author | Jun Lin Qinfeng Li Tingting Jin Jiacheng Wang Yingchao Gong Qingbo Lv Meihui Wang Jiawen Chen Min Shang Yanbo Zhao Guosheng Fu |
| author_facet | Jun Lin Qinfeng Li Tingting Jin Jiacheng Wang Yingchao Gong Qingbo Lv Meihui Wang Jiawen Chen Min Shang Yanbo Zhao Guosheng Fu |
| author_sort | Jun Lin |
| collection | DOAJ |
| description | Abstract Myocardial ischemia reperfusion (I/R) injury is a complex process with intense inflammatory response and cardiomyocyte apoptosis. As a decoy receptor of IL-1β, Interleukin-1 receptor type 2 (IL-1R2) inhibits IL-1β signaling. However, its role in I/R injury remains unknown. Here we found that the serum levels of IL-1R2 were significantly increased in patients with acute myocardial infarction (AMI) following interventional therapy. Similarly, after myocardial I/R surgery, IL-1R2 expression was significantly increased in heart of wild-type mice. In addition, IL-1R2-deficient mice heart showed enlarged infarct size, increased cardiomyocyte apoptosis together with reduced cardiac systolic function. Following exposure to hypoxia and reoxygenation (H/R), neonatal rat ventricular myocytes (NRVM) significantly increased IL-1R2 expression relying on NF-κB activation. Consistently, IL-1R2-deficient mice increased immune cells infiltrating into heart after surgery, which was relevant with cardiac damage. Additionally, IL-1R2 overexpression in cardiomyocyte protected cardiomyocyte against apoptosis through reducing the IL-17RA expression both in vivo and in vitro. Our results indicate that IL-1R2 protects cardiomyocytes from apoptosis, which provides a therapeutic approach to turn down myocardial I/R injury. |
| first_indexed | 2024-12-24T19:07:12Z |
| format | Article |
| id | doaj.art-e7d769cfd5f54594ac9c32bccd6dfad1 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-24T19:07:12Z |
| publishDate | 2022-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-e7d769cfd5f54594ac9c32bccd6dfad12022-12-21T16:43:04ZengNature Publishing GroupCell Death and Disease2041-48892022-01-0113111210.1038/s41419-022-04533-1Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosisJun Lin0Qinfeng Li1Tingting Jin2Jiacheng Wang3Yingchao Gong4Qingbo Lv5Meihui Wang6Jiawen Chen7Min Shang8Yanbo Zhao9Guosheng Fu10Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityAbstract Myocardial ischemia reperfusion (I/R) injury is a complex process with intense inflammatory response and cardiomyocyte apoptosis. As a decoy receptor of IL-1β, Interleukin-1 receptor type 2 (IL-1R2) inhibits IL-1β signaling. However, its role in I/R injury remains unknown. Here we found that the serum levels of IL-1R2 were significantly increased in patients with acute myocardial infarction (AMI) following interventional therapy. Similarly, after myocardial I/R surgery, IL-1R2 expression was significantly increased in heart of wild-type mice. In addition, IL-1R2-deficient mice heart showed enlarged infarct size, increased cardiomyocyte apoptosis together with reduced cardiac systolic function. Following exposure to hypoxia and reoxygenation (H/R), neonatal rat ventricular myocytes (NRVM) significantly increased IL-1R2 expression relying on NF-κB activation. Consistently, IL-1R2-deficient mice increased immune cells infiltrating into heart after surgery, which was relevant with cardiac damage. Additionally, IL-1R2 overexpression in cardiomyocyte protected cardiomyocyte against apoptosis through reducing the IL-17RA expression both in vivo and in vitro. Our results indicate that IL-1R2 protects cardiomyocytes from apoptosis, which provides a therapeutic approach to turn down myocardial I/R injury.https://doi.org/10.1038/s41419-022-04533-1 |
| spellingShingle | Jun Lin Qinfeng Li Tingting Jin Jiacheng Wang Yingchao Gong Qingbo Lv Meihui Wang Jiawen Chen Min Shang Yanbo Zhao Guosheng Fu Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis Cell Death and Disease |
| title | Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis |
| title_full | Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis |
| title_fullStr | Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis |
| title_full_unstemmed | Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis |
| title_short | Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis |
| title_sort | cardiomyocyte il 1r2 protects heart from ischemia reperfusion injury by attenuating il 17ra mediated cardiomyocyte apoptosis |
| url | https://doi.org/10.1038/s41419-022-04533-1 |
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