MicroRNA-146 regulates the inflammatory cytokines expression in vascular endothelial cells during sepsis.

AIMS

The purpose of this study was to investigate the functional role of microRNA (miR)-146 in sepsis, as well as the underlying mechanism.

METHODS

Human vascular endothelial cell line EA. hy926 cells were treated with lipopolysaccharide (LPS) and/or transfected with miR-146 mimics, inhibitor, and their corresponding controls. Expression of miR-146 was then analyzed after treatment and/or transfection, as well as the expression of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, and E-selectin, and nuclear factor kappa B (NF-κB) binding activity.

RESULTS

The results showed that the expression of miR-146 was significantly downregulated by LPS stimulation compared to the control group (P < 0.05). Also, the expression of miR-146 was remarkably increased by miR-146 mimics but decreased by miR-146 inhibitor following stimulation with LPS (P < 0.05). In addition, the expression levels of TNF-α, IL-6, ICAM-1, and E-selectin were shown to increase following induction by LPS, and further markedly elevated by miR-146 inhibitor (all P < 0.05). However, the expression levels of these inflammatory cytokines were outstandingly decreased by miR-146 mimics (all P < 0.05). Moreover, we observed that the relative NF-κB activity was statistically upregulated by miR-146 inhibitor but downregulated by miR-146 mimics.

CONCLUSIONS

MiR-146 may play an important role in the pathogenesis and development of sepsis by suppressing the expression of inflammatory cytokines.