Interleukin‐22 Directly Activates Myocardial STAT3 (Signal Transducer and Activator of Transcription‐3) Signaling Pathway and Prevents Myocardial Ischemia Reperfusion Injury

Author:

Takahashi Jinya1,Yamamoto Mai2,Yasukawa Hideo1ORCID,Nohara Shoichiro1,Nagata Takanobu1,Shimozono Koutatsu1,Yanai Toshiyuki1,Sasaki Tomoko1,Okabe Kota1,Shibata Tatsuhiro1,Mawatari Kazutoshi1,Kakuma Tatsuyuki3,Aoki Hiroki2,Fukumoto Yoshihiro12

Affiliation:

1. Division of Cardiovascular Medicine Department of Internal Medicine Kurume University School of Medicine Kurume Japan

2. Cardiovascular Research Institute Kurume University Kurume Japan

3. Biostatistics Center Kurume University Kurume Japan

Abstract

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 STAT 3 (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 STAT 3 activation after IL ‐22 injection by Western blot analysis and immunostaining for phosphorylated STAT 3 in the heart and found that STAT 3 activation in heart tissue rapidly peaked after IL ‐22 injection. Coimmunostaining of phosphorylated STAT 3 and α‐actinin revealed that STAT 3 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 STAT 3, 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– STAT 3 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 STAT 3 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 STAT 3 signaling pathway and acted as a cardioprotective cytokine to ameliorate acute myocardial infarction after ischemia reperfusion.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3