Interleukin-1β-stimulated macrophage-derived exosomes improve myocardial injury in sepsis via regulation of mitochondrial homeostasis: experimental research.

Abstract

BACKGROUND: The purpose of this study was to investigate the effects of interleukin-1β (IL-1β) stimulation on the protection of macrophage-derived exosomes miR-146a (M-IL-exo-146a) on sepsis-induced myocardial injury (SMI) in vitro and in vivo . MATERIALS AND METHODS: Macrophage-derived exosomes (M-exo) and IL-1β-stimulated macrophage exosomes (M-IL-exo) were isolated from macrophages of sepsis with or without IL-1β. The expressions of miR-146a in M-exo and M-IL-exo were detected by fluorescence quantitative PCR. Related molecular biology technologies were used to evaluate the role and mechanism of M-exo-146a and M-IL-exo-146a on SMI and the enhancing effect of IL-1β. RESULTS: Compared with M-exo, the expression of miR-146a in M-IL-exo was significantly increased. M-IL-exo-146a significantly alleviated SMI by decreasing the level of serum myocardial enzymes, serum and myocardial oxidative stress and cytokines, and improved myocardial mitochondrial imbalance. The mechanism responsible for IL-1β enhancing the production of IL-M-exo miR-146a was via JNK-1/2 signal pathway. The mechanism responsible for M-exo-IL-miR-146a protecting SMI was related to miR-146a inhibiting inflammatory response and mitochondrial function via MAPK4/Drp-1 signal pathway. CONCLUSIONS: This study provides a new strategy for the treatment of SMI by delivering M-IL-exo.