{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T10:07:48Z","timestamp":1781086068630,"version":"3.54.1"},"reference-count":59,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T00:00:00Z","timestamp":1491955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81200177"],"award-info":[{"award-number":["81200177"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The immune system plays an important role in driving the acute inflammatory response following myocardial ischaemia\/reperfusion injury (MIRI). IL\u201021 is a pleiotropic cytokine with multiple immunomodulatory effects, but its role in MIRI is not known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Myocardial injury, neutrophil infiltration and the expression of neutrophil chemokines KC (CXCL1) and MIP\u20102 (CXCL2) were studied in a mouse model of MIRI. Effects of IL\u201021 on the expression of KC and MIP\u20102 in neonatal mouse cardiomyocytes (CMs) and cardiac fibroblasts (CFs) were determined by real\u2010time PCR and ELISA. The signalling mechanisms underlying these effects were explored by western blot analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>IL\u201021 was elevated within the acute phase of murine MIRI. Neutralization of IL\u201021 attenuated myocardial injury, as illustrated by reduced infarct size, decreased cardiac troponin T levels and improved cardiac function, whereas exogenous IL\u201021 administration exerted opposite effects. IL\u201021 increased the infiltration of neutrophils and increased the expression of KC and MIP\u20102 in myocardial tissue following MIRI. Moreover, neutrophil depletion attenuated the IL\u201021\u2010induced myocardial injury. Mechanistically, IL\u201021 increased the production of KC and MIP\u20102 in neonatal CMs and CFs, and enhanced neutrophil migration, as revealed by the migration assay. Furthermore, we demonstrated that this IL\u201021\u2010mediated increase in chemokine expression involved the activation of Akt\/NF\u2010\u03baB signalling in CMs and p38 MAPK\/NF\u2010\u03baB signalling in CFs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our data provide novel evidence that IL\u201021 plays a pathogenic role in MIRI, most likely by promoting cardiac neutrophil infiltration. Therefore, targeting IL\u201021 may have therapeutic potential as a treatment for MIRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.8\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.8\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13781","type":"journal-article","created":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T01:06:44Z","timestamp":1489540004000},"page":"1329-1343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["IL\u201021 promotes myocardial ischaemia\/reperfusion injury through the modulation of neutrophil infiltration"],"prefix":"10.1111","volume":"175","author":[{"given":"Kejing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Key Laboratory of Biological 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