IL-33 attenuates anoxia/reoxygenation-induced cardiomyocyte apoptosis by inhibition of PKCβ/JNK pathway

• Published in: PloS one 2013-02, Vol.8 (2), p.e56089
• Main Authors: Rui, Tao, Tang, Qizhu
• Format: Article
• Language: English
• Subjects: Animals; Anoxia; Apoptosis; Apoptosis - drug effects; Attenuation; Biology; Cardiology; Cardiomyocytes; Cardiovascular disease; Caspase; Caspase-3; Cells, Cultured; Cytokines; Deoxyribonucleic acid; Diabetes; DNA; Gene Deletion; Heart attacks; Heart diseases; Hospitals; Hypoxia - drug therapy; Hypoxia - metabolism; Inhibition; Interleukin 1; Interleukin-33; Interleukins - therapeutic use; Ischemia; JNK protein; Kinases; Laboratory animals; MAP Kinase Signaling System - drug effects; Medicine; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 8 - genetics; Mitogen-Activated Protein Kinase 8 - metabolism; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Myocytes; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation; Phosphorylation - drug effects; Protein kinase C; Protein Kinase C - genetics; Protein Kinase C - metabolism; Protein Kinase C beta; Proteins; RNA Interference; RNA, Small Interfering - genetics; Rodents; siRNA; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056089

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. 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; PKCβII and JNK phosphorylation were assessed with Western blot. Challenge of cardiomyocytes with an A/R resulted in cardiomyocyte oxidative stress, PKCβII and JNK phosphorylation, and myocyte apoptosis. Treatment of the cardiomyocytes with IL-33 attenuated the A/R-induced myocyte oxidative stress, prevented PKCβII 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 PKCβII or myocytes deficient in JNK1. Inhibition of PKCβII prevented the A/R-induced JNK phosphorylation, but inhibition of JNK1 showed no effect on A/R-induced PKCβII phosphorylation. Our results indicate that IL-33 prevents the A/R-induced myocyte apoptosis through inhibition of PKCβ/JNK pathway.