| Autor: |
Barry, S. P., Ounzain, S., Mccormick, J., Scarabelli, T. M., Chen Scarabelli, C., L. I. I., Faggian, Giuseppe, Mazzucco, Alessandro, Suzuki, Hisanori, Thiemermann, C., Knight, R. A., Latchman, D. S., Stephanou, A. |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
International Journal of Cardiology. 163(3):326-334 |
| ISSN: |
0167-5273 |
| DOI: |
10.1016/j.ijcard.2011.08.849 |
| Popis: |
BackgroundIL-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.MethodsIn 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.ResultsExpression 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.ConclusionsThese 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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