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.
Subject(s)
HMGB1 Protein/metabolism , Interleukin-33/physiology , MAP Kinase Signaling System , Myocardial Ischemia/immunology , Animals , Apoptosis , Cells, Cultured , Gene Expression , HMGB1 Protein/genetics , Male , Myocytes, Cardiac , Protective Factors , Rats, Sprague-Dawley , Up-RegulationABSTRACT
Objective To investigate the protective mechanism of Interleukin 33 (IL-33) in preventing myocardial ischemia and reperfusion injury in rats. Methods A rat model with myocardial I/R with 32the adult male SD rats , which were randomly divided into 4 groups: SO group , I/R group , IL-33 + I/R group , SB230580 + IL-33 + I/R group. The levels of LDH, CK, TNF-α, IL-6, HMGB1, Bcl-2, total caspase-3, cleaved caspase-3 and P-P38 were detected. Results After reperfusion, IL-33 significantly decreased the levels of serum LDH and CK and the expression of TNF-α, IL-6 , cleaved caspase-3 , but significantly increased the expressions of Bcl-2, p-P38 (P < 0.05). SB230580 attenuated the protective role of IL-33 on myocardial I/R in a certain degree. Conclusions IL-33 may prevent myocardial I/R injury via inhibiting inflammation and cardiocyteapoptosis by way of P38 MAPK signaling pathway.