Abstract
Interleukin-33 (IL-33) plays a protective role in myocardial ischemia and reperfusion (I/R) injury, but the underlying mechanism was not fully elucidated. The present study was designed to investigate whether IL-33 protects against myocardial I/R injury by regulating both P38 mitogen-activated-protein kinase (P38 MAPK), which is involved in one of the downstream signaling pathways of IL-33, and high mobility group box protein 1 (HMGB1), a late pro-inflammatory cytokine. Myocardial I/R injury increased the level of IL-33 and its induced receptor (sST) in myocardial tissue. Compared with the I/R group, the IL-33 group had significantly lower cardiac injury (lower serum creatine kinase (CK), lactate dehydrogenase (LDH), and cTnI levels and myocardial infarct size), a suppressed inflammatory response in myocardial tissue (lower expression of HMGB1, IL-6, TNF-α and INF-γ) and less myocardial apoptosis (much higher Bcl-2/Bax ratio and lower cleaved caspase-3 expression). Moreover, IL-33 activated the P38 MAPK signaling pathway (up-regulating P-P38 expression) in myocardial tissue, and SB230580 partially attenuated the anti-inflammatory and anti-apoptosis effects of IL-33. These findings indicated that IL-33 protects against myocardial I/R injury by inhibiting inflammatory responses and myocardial apoptosis, which may be associated with the HMGB1 and P38 MAPK signaling pathways.
Highlights
Myocardial reperfusion therapies, which are the most effective treatments for acute myocardial infarction, include percutaneous coronary intervention (PCI), thrombolytic therapy and coronary artery bypass grafts (CABGs)
We hypothesize that IL-33 protects against myocardial ischemia and reperfusion (I/R) injury by inhibiting inflammatory responses, including high mobility group box protein 1 (HMGB1) expression
These findings indicated that IL-33 inhibited myocardial apoptosis during I/R injury, which is consistent with the findings of previous studies [6,7]
Summary
Animal Preparation and Experimental DesignAll experimental protocols in this study conformed to the Guidelines for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication, revised 1996) and were approved by the Renmin Hospital of Wuhan University. The rats were treated with sterile saline (0.5ml per rat, i.v., tail vein). Ischemia and reperfusion + sterile saline (I/R) (n = 10): rats were subjected to left anterior descending coronary artery (LAD) occlusion for 30 min followed by reperfusion for 4 h. The rats were treated with sterile saline (0.5ml per rat, i.v., tail vein) 30 minutes before LAD occlusion. IL-33+I/R (IL-33+I/R) (n = 6): rats were subjected to LAD occlusion for 30 min followed by reperfusion for 4 h. The rats were treated with IL-33 (10 μg per rat, i.v., tail vein, PEPROTECH, USA) [8] 30 minutes before LAD occlusion.
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