IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation

Abstract Background Reperfusion therapy is the most effective approach to resolve coronary occlusion, but myocardial injury caused by excessive inflammation during myocardial ischemia–reperfusion will also pose a new threat to health. Our prior study revealed the expression pattern of interleukin‐38...

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Main Authors: Yuzhen Wei, Junhui Xing, Xin Su, Xiangrao Li, Xiaofei Yan, Jiangtao Zhao, Hailong Tao
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:Immunity, Inflammation and Disease
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Online Access:https://doi.org/10.1002/iid3.898
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author Yuzhen Wei
Junhui Xing
Xin Su
Xiangrao Li
Xiaofei Yan
Jiangtao Zhao
Hailong Tao
author_facet Yuzhen Wei
Junhui Xing
Xin Su
Xiangrao Li
Xiaofei Yan
Jiangtao Zhao
Hailong Tao
author_sort Yuzhen Wei
collection DOAJ
description Abstract Background Reperfusion therapy is the most effective approach to resolve coronary occlusion, but myocardial injury caused by excessive inflammation during myocardial ischemia–reperfusion will also pose a new threat to health. Our prior study revealed the expression pattern of interleukin‐38 (IL‐38) in the peripheral blood serum of patients with ischemic cardiomyopathy and the role of IL‐38 in acute myocardial infarction in mice. However, its role and potential mechanisms in myocardial ischemia/reperfusion injury (MIRI) remain to be determined. Methods and Results The left anterior descending artery of C57BL/6 mice was transiently ligated to induce the MIRI model. We found that MIRI induced the expression of endogenous IL‐38, which was mainly produced by locally infiltrating macrophages. Overexpression of IL‐38 in C57BL/6 mice attenuated inflammatory injury and decreased myocardial apoptosis after myocardial ischemia–reperfusion. Furthermore, IL‐38 inhibited lipopolysaccharide‐induced macrophage inflammation in vitro. Cardiomyocytes cocultured with the supernatant of IL‐38‐ and troponin I‐treated macrophages showed a lower rate of apoptosis than controls. Conclusions IL‐38 attenuates MIRI by inhibiting macrophage inflammation. This inhibitory effect may be partially achieved by inhibiting the activation of NOD‐like receptor pyrin domain‐related protein 3 inflammasome, resulting in decreased expression of inflammatory factors and reduced cardiomyocyte apoptosis.
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spelling doaj-art-26166c1a4e1045419432a73b5edf697d2025-08-20T03:54:07ZengWileyImmunity, Inflammation and Disease2050-45272023-06-01116n/an/a10.1002/iid3.898IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammationYuzhen Wei0Junhui Xing1Xin Su2Xiangrao Li3Xiaofei Yan4Jiangtao Zhao5Hailong Tao6Department of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaAbstract Background Reperfusion therapy is the most effective approach to resolve coronary occlusion, but myocardial injury caused by excessive inflammation during myocardial ischemia–reperfusion will also pose a new threat to health. Our prior study revealed the expression pattern of interleukin‐38 (IL‐38) in the peripheral blood serum of patients with ischemic cardiomyopathy and the role of IL‐38 in acute myocardial infarction in mice. However, its role and potential mechanisms in myocardial ischemia/reperfusion injury (MIRI) remain to be determined. Methods and Results The left anterior descending artery of C57BL/6 mice was transiently ligated to induce the MIRI model. We found that MIRI induced the expression of endogenous IL‐38, which was mainly produced by locally infiltrating macrophages. Overexpression of IL‐38 in C57BL/6 mice attenuated inflammatory injury and decreased myocardial apoptosis after myocardial ischemia–reperfusion. Furthermore, IL‐38 inhibited lipopolysaccharide‐induced macrophage inflammation in vitro. Cardiomyocytes cocultured with the supernatant of IL‐38‐ and troponin I‐treated macrophages showed a lower rate of apoptosis than controls. Conclusions IL‐38 attenuates MIRI by inhibiting macrophage inflammation. This inhibitory effect may be partially achieved by inhibiting the activation of NOD‐like receptor pyrin domain‐related protein 3 inflammasome, resulting in decreased expression of inflammatory factors and reduced cardiomyocyte apoptosis.https://doi.org/10.1002/iid3.898interleukin‐38macrophagesmyocardial apoptosismyocardial ischemia–reperfusion injury
spellingShingle Yuzhen Wei
Junhui Xing
Xin Su
Xiangrao Li
Xiaofei Yan
Jiangtao Zhao
Hailong Tao
IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation
Immunity, Inflammation and Disease
interleukin‐38
macrophages
myocardial apoptosis
myocardial ischemia–reperfusion injury
title IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation
title_full IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation
title_fullStr IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation
title_full_unstemmed IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation
title_short IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation
title_sort il 38 attenuates myocardial ischemia reperfusion injury by inhibiting macrophage inflammation
topic interleukin‐38
macrophages
myocardial apoptosis
myocardial ischemia–reperfusion injury
url https://doi.org/10.1002/iid3.898
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AT xinsu il38attenuatesmyocardialischemiareperfusioninjurybyinhibitingmacrophageinflammation
AT xiangraoli il38attenuatesmyocardialischemiareperfusioninjurybyinhibitingmacrophageinflammation
AT xiaofeiyan il38attenuatesmyocardialischemiareperfusioninjurybyinhibitingmacrophageinflammation
AT jiangtaozhao il38attenuatesmyocardialischemiareperfusioninjurybyinhibitingmacrophageinflammation
AT hailongtao il38attenuatesmyocardialischemiareperfusioninjurybyinhibitingmacrophageinflammation