MicroRNA-451 relieves inflammation in cerebral ischemia-reperfusion via the Toll-like receptor 4/MyD88/NF-κB signaling pathway

Abstract

The present study was designed to investigate the role of microRNA-451 (miRNA-451) on cerebral ischemia-reperfusion and to explore its possible mechanism. The expression of miRNA-451 was downregulated in rats with cerebral ischemia-reperfusion. In an in vitro model of cerebral ischemia-reperfusion, the downregulation of miRNA-451 increased inflammation, demonstrated by increased levels of tumor necrosis factor α, interleukin (IL)-lb, IL-6 and IL-18. However, the upregulation of miRNA-451 expression decreased inflammation in the same in vitro model of cerebral ischemia-reperfusion. In addition, it was found that the downregulation of miRNA-451 induced the expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88 (MyD88) and nuclear factor-κB (NF-κB)/p65. Moreover, the administration of a MyD88 inhibitor, ST 2825, reduced the expression of MyD88 and NF-κB/p65 in the in vitro model of cerebral ischemia-reperfusion, inhibiting the effects of miRNA-451 upregulation on inflammation. A TLR4 inhibitor, TAK-242, was used to reduce the expression of TLR4 in the in vitro model of cerebral ischemia-reperfusion. TAK-242 suppressed the effects of miRNA-451 downregulation on inflammation. The present study suggested that miRNA-451 regulated cerebral ischemia-reperfusion-induced inflammation, which is mediated through the TLR4/MyD88/NF-κB signaling pathway.