Interleukin-22 Directly Activates Myocardial STAT3 (Signal Transducer and Activator of Transcription-3) Signaling Pathway and Prevents Myocardial Ischemia Reperfusion Injury
BACKGROUND Interleukin (IL)-22, a member of the IL-10 cytokine family, is the only known cytokine that is secreted by immune cells but does not target immune cells; it mainly targets epithelial cells. In this study, we aimed to determine whether IL-22 administration could activate the myocardial STA...
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Published in | Journal of the American Heart Association Vol. 9; no. 8; p. e014814 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
John Wiley and Sons Inc
21.04.2020
Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | BACKGROUND Interleukin (IL)-22, a member of the IL-10 cytokine family, is the only known cytokine that is secreted by immune cells but does not target immune cells; it mainly targets epithelial cells. In this study, we aimed to determine whether IL-22 administration could activate the myocardial STAT3 (signal transducer and activator of transcription-3) signaling pathway, and thus prevent myocardial injury, in a mouse model of ischemia reperfusion injury. METHODS AND RESULTS We evaluated the STAT3 activation after IL-22 injection by Western blot analysis and immunostaining for phosphorylated STAT3 in the heart and found that STAT3 activation in heart tissue rapidly peaked after IL-22 injection. Coimmunostaining of phosphorylated STAT3 and α-actinin revealed that STAT3 activation occurred in cardiomyocytes after IL-22 administration. In heart tissue from intact mice, real-time PCR demonstrated significant expression of IL-22 receptor subunit 1, and coimmunostaining of IL-22 receptor subunit 1 and α-actinin showed IL-22 receptor subunit 1 expression in cardiomyocytes. In cultured cardiomyocytes, IL-22 activated STAT3, and we detected IL-22 receptor subunit 1 expression. Overall, these results indicated that IL-22 directly activated the myocardial IL-22-receptor subunit 1-STAT3 signaling pathway. Following ischemia reperfusion, compared with PBS-treated mice, IL-22-treated mice exhibited a significantly reduced infarct size, significantly reduced myocardial apoptosis, and significantly enhanced phosphorylated STAT3 expression. Moreover, heart tissue from IL-22-treated mice exhibited a significantly reduced expression ratio of phosphorylated p53 to p53. CONCLUSIONS Our present findings suggest that IL-22 directly activated the myocardial STAT3 signaling pathway and acted as a cardioprotective cytokine to ameliorate acute myocardial infarction after ischemia reperfusion. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 For Sources of Funding and Disclosures, see page 15. |
ISSN: | 2047-9980 2047-9980 |
DOI: | 10.1161/JAHA.119.014814 |