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)-1b, 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.

Understanding the Connection Between Common Stroke Comorbidities, Their Associated Inflammation, and the Course of the Cerebral Ischemia/Reperfusion Cascade

“…As a result of the activation of the aforementioned receptors, the transcription factor NF-kB (nuclear factor kappa B) triggers the expression of genes encoding pro-inflammatory molecules, including IL-1b (interleukin-1b), IL-6, IL-8 (interleukin 8), IL-18 (interleukin 18), and TNF-a. Another activated transcription factor involved in the expression of pro-inflammatory genes is AP-1 (activator protein 1), an important activator of IL-1 and TNF-a expression and the promotion of the expression of some adhesion molecules (50)(51)(52). The path from TLR4 receptors to NF-kB and AP-1 activation is mainly through the MyD88 protein (myeloid differentiation primary response protein) (53,54).…”

Increased expression of pro‐inflammatory cytokines at the fetal–maternal interface in bovine pregnancies produced by cloning

“… 62 This miRNA inhibits NF‐κB activity and consequently downregulates pro‐inflammatory molecules in several tissues. 63 , 64 , 65 Here, we observed a downregulation of miR‐451 in the MHC‐I heterozygous incompatible pregnancies, which suggests this microRNA is involved in the development of a pro‐inflammatory environment at the fetal–maternal interface. No other hypoxia‐specific miRNAs are among the differentially regulated miRNAs found in this study, suggesting the downregulation of miR‐451 is not due to hypoxia, but rather to other mechanisms.…”

Polyphenolics from Syzygium brachythyrsum Inhibits Oxidized Low-Density Lipoprotein-Induced Macrophage-Derived Foam Cell Formation and Inflammation

“…Evidence suggested that NF-κB and MAPK pathways are typical pro-inflammatory signaling pathways involved in inflammation and lipid accumulation [ 23 , 24 ]. In addition, TLR4 activation can bind to the TLR structural domain of MyD88 and trigger a series of phosphorylation reactions to activate NF-κB kinase, thereby activating NF-κB [ 25 , 26 , 27 ] and ultimately promoting the production of TNF-α, IL-6, and IL-β [ 28 , 29 , 30 ]. Based on these studies, we investigated the expression of key proteins in the NF-κB and MAPK pathways in ox-LDL-induced foam cells.…”