{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:26:39Z","timestamp":1790814399851,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,4,21]]},"abstract":"\n BACKGROUND<\/jats:title>\n \n Interleukin (\n IL<\/jats:styled-content>\n )\u201022, a member of the\n IL<\/jats:styled-content>\n \u201010 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\n IL<\/jats:styled-content>\n \u201022 administration could activate the myocardial\n STAT<\/jats:styled-content>\n 3 (signal transducer and activator of transcription\u20103) signaling pathway, and thus prevent myocardial injury, in a mouse model of ischemia reperfusion injury.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS AND RESULTS<\/jats:title>\n \n We evaluated the\n STAT<\/jats:styled-content>\n 3 activation after\n IL<\/jats:styled-content>\n \u201022 injection by Western blot analysis and immunostaining for phosphorylated\n STAT<\/jats:styled-content>\n 3 in the heart and found that\n STAT<\/jats:styled-content>\n 3 activation in heart tissue rapidly peaked after\n IL<\/jats:styled-content>\n \u201022 injection. Coimmunostaining of phosphorylated\n STAT<\/jats:styled-content>\n 3 and \u03b1\u2010actinin revealed that\n STAT<\/jats:styled-content>\n 3 activation occurred in cardiomyocytes after\n IL<\/jats:styled-content>\n \u201022 administration. In heart tissue from intact mice, real\u2010time\n PCR<\/jats:styled-content>\n demonstrated significant expression of\n IL<\/jats:styled-content>\n \u201022 receptor subunit 1, and coimmunostaining of\n IL<\/jats:styled-content>\n \u201022 receptor subunit 1 and \u03b1\u2010actinin showed\n IL<\/jats:styled-content>\n \u201022 receptor subunit 1 expression in cardiomyocytes. In cultured cardiomyocytes,\n IL<\/jats:styled-content>\n \u201022 activated\n STAT<\/jats:styled-content>\n 3, and we detected\n IL<\/jats:styled-content>\n \u201022 receptor subunit 1 expression. Overall, these results indicated that\n IL<\/jats:styled-content>\n \u201022 directly activated the myocardial\n IL<\/jats:styled-content>\n \u201022\u2010receptor subunit 1\u2013\n STAT<\/jats:styled-content>\n 3 signaling pathway. Following ischemia reperfusion, compared with\n PBS<\/jats:styled-content>\n \u2010treated mice,\n IL<\/jats:styled-content>\n \u201022\u2010treated mice exhibited a significantly reduced infarct size, significantly reduced myocardial apoptosis, and significantly enhanced phosphorylated\n STAT<\/jats:styled-content>\n 3 expression. Moreover, heart tissue from\n IL<\/jats:styled-content>\n \u201022\u2010treated mice exhibited a significantly reduced expression ratio of phosphorylated p53 to p53.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n \n Our present findings suggest that\n IL<\/jats:styled-content>\n \u201022 directly activated the myocardial\n STAT<\/jats:styled-content>\n 3 signaling pathway and acted as a cardioprotective cytokine to ameliorate acute myocardial infarction after ischemia reperfusion.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.014814","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T05:06:26Z","timestamp":1587099986000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Interleukin\u201022 Directly Activates Myocardial STAT3 (Signal Transducer and Activator of Transcription\u20103) Signaling Pathway and Prevents Myocardial Ischemia Reperfusion Injury"],"prefix":"10.1161","volume":"9","author":[{"given":"Jinya","family":"Takahashi","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine Department of Internal Medicine Kurume University School of Medicine Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Kurume University Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0422-1145","authenticated-orcid":false,"given":"Hideo","family":"Yasukawa","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Department of Internal Medicine Kurume University School of Medicine Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoichiro","family":"Nohara","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Department of Internal Medicine 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