The role of dendritic cells regulated by HMGB1/TLR4 signalling pathway in myocardial ischaemia reperfusion injury.

Inflammatory response plays an important role in ischaemia reperfusion injury (IRI) through a variety of inflammatory cells. Apart from neutrophils, macrophages and lymphocytes, the role of dendritic cells (DCs) in IRI has been noticed. The study was aimed at investigating whether the high-mobility group protein box-1/toll like receptor 4 (HMGB1/TLR4) signalling pathway regulate the migration, adhesion and aggregation of DCs to the myocardium, induce DCs activation and maturation, stimulate the expression of surface costimulatory molecules and participate in myocardial IRI. In vivo, migration, adhesion, and aggregation of DCs was enhanced; the expression of peripheral blood DCs CD80 and CD86, myocardial adhesion molecules were increased; and the infarct size was increased during myocardial ischaemia reperfusion injury myocardial ischemic/reperfusion injury (MI/RI). These responses induced by MI/RI were significantly inhibited by HMGB1 specific neutralizing antibody treatment. Cellular experiments confirmed that HMGB1 promoted the release of inflammatory cytokines through TLR4/MyD88/NF-κB, upregulated CD80 and CD86 expression, mediated the damage of cardiomyocytes and accelerated the apoptosis. Our results indicate that DCs activation and maturation, stimulate the expression of surface costimulatory molecules by promoting the release of inflammatory factors through NF-κB pathway and participate in myocardial IRI.