MiR-124 Promotes Microglial M2 Polarization Through TLR4/MyD88/NF-κB p65/NLRP3 Signaling In Palmitic Acid Treated-BV2 Cells

Abstract Aim Neuroinflammation is an explanation why obesity or high-fat diet induce central nervous system disorders. MiR-124, as a highly expressed microRNA in brain, might alleviate neuroinflammation through regulating microglial M1/M2 polarization, but its mechanism is unclear. The aim of the study was to explore whether miR-124 exerted its effect mentioned above through TLR4/MyD88/NF-κB p65/NLRP3 signaling in palmitic acid treated-microglia. Methods Prepared BV2 cells were treated with palmitic acid to establish an in vitro model of high-fat diet. MiR-124 mimic and inhibitor were adopted to up-regulate and down-regulate the expression of miR-124. TAK-242 and NLRP3 siRNA were used to down-regulate the expression of TLR4 and NLRP3. Expression of miR-124, signaling proteins (TLR4, MyD88, NF-κB p65), inflammasome markers (NLRP3, IL-1β) and microglial polarization markers (CD206, Arg-1, CD86, iNOS) was measured by qPCR and western blotting. Pyroptosis rate was assessed using flow cytometry. Results First, palmitic acid up-regulated the TLR4/MyD88/NF-κB p65 signaling, increased the NLRP3 expression, elevated the pyroptosis rate and inhibited the M2 polarization in BV2 cells. Second, miR-124 mimic and inhibitor separately alleviated and aggravated the effect of palmitic acid on microglial polarization and NLRP3 expression. MiR-124 mimic also down-regulated the TLR4/MyD88/NF-κB p65 signaling. Third, TAK-242 did not affect the expression of miR-124, but can simulate the protective effect of miR-124 mimic on microglial polarization and NLRP3 expression. Fourth, NLRP3 siRNA can also promoted M2 polarization in BV2 cells. Conclusion MiR-124 promoted microglial M2 polarization through TLR4/MyD88/NF-κB p65/NLRP3 signaling in palmitic acid treated-BV2 cells