Interleukin-22 alleviates Angiotensin II-induced cardiomyocyte apoptosis by preventing the intrinsic mitochondrial pathway

Abstract

Background Cardiac apoptosis plays an important role in the development of heart failure, and Angiotensin II (Ang II) plays a central role in the pathogenesis of RAAS-triggered cardiac apoptosis. Interleukin (IL)-22 is an inflammatory cytokine, which is involved in cardiovascular diseases. Recent evidence has demonstrated that there is a close relationship between IL-22 and human hypertension. However, the effects of IL-22 on Ang II-induced cardiomyocyte apoptosis remain unknown. Methods MCM cells and primary cardiomyocytes were exposed to Ang II with or without IL-22. The activation of the apoptosis signaling pathways, reactive oxygen species (ROS), supernatant TNF-α, Fas/FsaL, mitochondrial membrane potential (MMP), cytochrome c (Cyc) and the activity of superoxide diamutase (SOD) were detected. Results In MCM cells and primary cardiomyocytes, flow cytometry revealed that IL-22 significantly alleviated Ang II-induced apoptosis, and IL-22 receptors (IL-22R1 and IL-10R1) levels were obviously increased. Western blotting revealed that increased cleaved Caspase 3/8 and Bax protein levels were clearly reduced after IL-22 treatment. The Fas/FsaL and TNF-α levels were identical in the cells with or without IL-22 treatment. But ROS levels were markedly reduced after IL-22 treatment via upregulation of SOD activity, and Ang II-induced decrease of MMP was improved by IL-22, reducing the release of Cyc and the levels of cleaved Caspase 9. Conclusions IL-22 improved Ang II-induced cardiomyocyte apoptosis via inhibiting the intrinsic apoptosis pathway.