miR-181a and miR-150 regulate dendritic cell immune inflammatory responses and cardiomyocyte apoptosis via targeting JAK1- STAT1/c-Fos pathway.

The immune inflammatory response plays a crucial role in many cardiac pathophysiological processes, including ischaemic cardiac injury and the post-infarction repair process. Micro RNAs (mi RNAs) regulate the development and function of dendritic cells ( DCs), which are key players in the initiation and regulation of immune responses; however, the underlying regulatory mechanisms remain unclear. Here, we used the supernatants of necrotic primary cardiomyocytes (Necrotic-S) to mimic the myocardial infarction ( MI) microenvironment to investigate the role of mi RNAs in the regulation of DC-mediated inflammatory responses. Our results showed that Necrotic-S up-regulated the DC maturation markers CD40, CD83 and CD86 and increased the production of inflammatory cytokines, concomitant with the up-regulation of miR-181a and down-regulation of miR-150. Necrotic-S stimulation activated the JAK/ STAT pathway and promoted the nuclear translocation of c-Fos and NF-κB p65, and silencing of STAT1 or c-Fos suppressed Necrotic-S-induced DC maturation and inflammatory cytokine production. The effects of Necrotic-S on DC maturation and inflammatory responses, its activation of the JAK/ STAT pathway and the induction of cardiomyocyte apoptosis under conditions of hypoxia were suppressed by miR-181a or miR-150 overexpression. Taken together, these data indicate that miR-181a and miR-150 attenuate DC immune inflammatory responses via JAK1- STAT1/c-Fos signalling and protect cardiomyocytes from cell death under conditions of hypoxia. [ABSTRACT FROM AUTHOR]