IL-33 Attenuates Anoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Inhibition of PKCβ/JNK Pathway

Background: Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family. The objectives of present study are to assess whether IL-33 can protect cardiomyocytes from anoxia/reoxygenation (A/R)-induced injury and the mechanism involved in the protection. Methods: Cardiomyocytes derived from either wild type or JNK1(-/-) mice were challenged with an A/R with or without IL-33. Myocyte apoptosis was assessed by measuring caspase 3 activity, fragmented DNA and TUNEL staining. In addition, cardiomyocyte oxidative stress was assessed by measuring DHR123 oxidation; PKC beta II and JNK phosphorylation were assessed with Western blot. Results: Challenge of cardiomyocytes with an A/R resulted in cardiomyocyte oxidative stress, PKC beta II and JNK phosphorylation, and myocyte apoptosis. Treatment of the cardiomyocytes with IL-33 attenuated the A/R-induced myocyte oxidative stress, prevented PKC beta II and JNK phosphorylation and attenuated the A/R-induced myocyte apoptosis. The protective effect of the IL-33 did not show in cardiac myocytes with siRNA specific to PKC beta II or myocytes deficient in JNK1. Inhibition of PKC beta II prevented the A/R-induced JNK phosphorylation, but inhibition of JNK1 showed no effect on A/R-induced PKC beta II phosphorylation. Conclusions: Our results indicate that IL-33 prevents the A/R-induced myocyte apoptosis through inhibition of PKC beta/JNK pathway.