Enhanced IL-17 signalling following myocardial ischaemia/reperfusion injury

• Published in: International journal of cardiology 2013-03, Vol.163 (3), p.326-334
• Main Authors: Barry, Seán P, Ounzain, Samir, McCormick, James, Scarabelli, Tiziano M, Chen-Scarabelli, Carol, Saravolatz, Louis I.I, Faggian, Giuseppe, Mazzucco, Alessandro, Suzuki, Hisanori, Thiemermann, Christoph, Knight, Richard A, Latchman, David S, Stephanou, Anastasis
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Apoptosis - physiology; Biological and medical sciences; Biomarkers - metabolism; Cardiology. Vascular system; Cardiovascular; Cells, Cultured; Coronary heart disease; Heart; Inflammation Mediators - physiology; Interleukin-17 - physiology; Male; Medical sciences; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocarditis. Cardiomyopathies; Myocytes, Cardiac - pathology; Myocytes, Cardiac - physiology; Rats; Rats, Sprague-Dawley; Rats, Wistar; Signal Transduction - physiology
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2011.08.849

Abstract Background IL-17A and IL-17F are pro-inflammatory cytokines which induce the expression of several cytokines, chemokines and matrix metalloproteinases (MMPs) in target cells. IL-17 cytokines have recently attracted huge interest due to their pathogenic role in diseases such as arthritis and inflammatory bowel disease although a role for IL-17 cytokines in myocardial infarction (MI) has not previously been described. Methods In vivo MI was performed by coronary artery occlusion in the absence or presence of a neutralizing IL-17 antibody for blocking IL-17 actions in vivo . IL-17 signaling was also assessed in isolated primary cardiomyocytes by Western blot, mRNA expression and immunostaining. Results Expression of IL-17A, IL-17F and the IL-17 receptor (IL-17RA) were all increased following MI. Expression of several IL-17 target genes, including Cxcl1, Cxcl2, IL-1β, iNOS and IL-6 was also upregulated following MI. In addition, IL-17A promoted the expression of Cxcl1 and IL-6 in isolated cardiomyocytes in a MAPK and PI(3)K-dependent manner. IL-17A and ischaemia/reperfusion (I/R) injury were found to have an additive effect on Cxcl1 expression, suggesting that IL-17 may enhance myocardial neutrophil recruitment during MI. Moreover, protein levels of both IL-17R and IL-17A were enhanced following in vivo MI. Finally, blocking IL-17 signaling in vivo reduced the levels of apoptotic cell death markers following in vivo MI. Conclusions These data imply that the expression of IL-17 cytokines and their receptor are elevated during myocardial I/R injury and may play a fundamental role in post infarct inflammatory and apoptotic responses.