IL-39 increases ROS production and promotes the phosphorylation of p38 MAPK in the apoptotic cardiomyocytes.

Abstract

The cytokine interleukin (IL)-39 is a novel member of the IL-12 family. Our previous study found that the serum level of IL-39 significantly increased in patients with acute myocardial infarction. However, the role of IL-39 in cardiomyocyte apoptosis remains unclear. In this study, the cultured mouse HL-1 cardiomyocytes were incubated with PBS, 0-100 ng/mL IL-39, 200 μM H2O2 or 20 μM Trolox. IL-39 promoted the production of intracellular reactive oxygen species (ROS) in a concentration dependent manner in HL-1 cardiomyocytes. IL-39 and H2O2 both significantly promoted the production of intracellular ROS, increased the level of intracellular CCL2, stimulated the apoptotic progress of cardiomyocytes, increased the mRNA and protein expression levels of Bax, caspase-3, and p-p38 MAPK, and decreased the mRNA and protein expression levels of Bcl-2. ROS production, CCL2 level, cardiomyocyte apoptosis, and expression of Bax, caspase-3, and p-p38 MAPK were significantly amplified by the administration of IL-39 combined with H2O2, and these processes were significantly alleviated by an antioxidant Trolox. This study was novel in revealing that IL-39 promoted apoptosis by stimulating the phosphorylation of p38 MAPK in mouse HL-1 cardiomyocytes.