Interleukin 32 participates in cardiomyocyte-induced oxidative stress, inflammation and apoptosis during hypoxia/reoxygenation via the NOD2/NOX2/MAPK signaling pathway

Although reperfusion of the ischemic myocardium has been used as a vital treatment of various patients with cardiovascular disease, the accompanying myocardial ischemia-reperfusion injury (MIRI) can cause further damage, resulting in a poor prognosis. The present study aimed to explore the roles and regulatory mechanisms of interleukin (IL)-32, a pro-inflammatory cytokine, in MIRI. Cardiomyocytes were subjected to hypoxia and reoxygenation (H/R) to mimic MIRI. The effects of IL-32 on oxidative stress, inflammation and apoptosis of H/R-treated cells were assessed. Given that the nucleotide-binding oligomerization domain 2 (NOD2) and NADPH oxidase 2 (NOX2) play roles in the inflammatory response and myocardial ischemia, the role of this regulatory axis in the function of IL-32 was evaluated. The results indicated that IL-32 levels were elevated following H/R treatment. Downregulation of IL-32 expression attenuated H/R-induced reduction in cell viability, LDH release, oxidative stress, inflammation and apoptosis. Moreover, downregulation of IL-32 expression reversed the activation of the NOD2/NOX2/MAPK signaling pathway caused by H/R treatment. NOD2 overexpression altered the effects of the downregulation of IL-32 expression on the cells, indicating that this regulatory axis mediated the function of IL-32. Collectively, the data indicated that IL-32 participated in the induction of oxidative stress, inflammation, and apoptosis in cardiomyocytes during H/R treatment via the NOD2/NOX2/MAPK signaling pathway.

Automated summary

IL-32 plays a pro-inflammatory role in myocardial ischemia-reperfusion injury and induces oxidative stress, inflammation, and apoptosis via the NOD2/NOX2/MAPK signaling pathway.