Apelin‑13 ameliorates LPS‑induced BV‑2 microglia inflammatory response through promoting autophagy and inhibiting H3K9ac enrichment of TNF‑α and IL‑6 promoter
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Abstract

Microglia is activated and polarized to pro‑inflammatory M1 phenotype or anti‑inflammatory M2 phenotype in neuroinflammation. Apelin‑13 exerts protective properties against neuroinflammation in several neurological disorders. We aimed to investigate whether apelin‑13 played a protective role on BV‑2 microglia and explore its underlying mechanisms. Lipopolysaccharide (LPS)‑stimulated BV‑2 microglia cells were treated with apelin‑13. Microglia activation was evaluated by immunofluorescence with F‑actin. Western blot was performed to measure the expression of autophagy associated proteins. CD16/32 and CD206 were detected to assess microglia polarization by western blot and flow cytometry. qRT‑PCR was utilized to measure inducible nitric oxide synthase (iNOS), arginase‑1 (Arg‑1), interleukin‑10 (IL‑10), interleukin‑6 (IL‑6) and tumor necrosis factor‑alpha (TNF‑α). Histone H3 acetyl lysine 9 (H3K9ac) enrichment of TNF‑α and IL‑6 promoter was detected by ChIP. We discovered that apelin‑13 impacted the actin cytoskeleton, recovering the control phenotype following LPS exposure. Apelin‑13 improved autophagy‑mediated microglia polarization towards M2 phenotype to alleviate inflammatory response in LPS‑stimulated cells. Autophagy flux inhibitor chloroquine antagonized these effects of apelin‑13 on LPS‑stimulated cells. Besides, apelin‑13 decreased the enrichment of H3K9ac at the promoter region of TNF‑α and IL‑6 to inhibit inflammatory response, which was reversed by histone deacetylase antagonist valproate. Taken together, apelin‑13 alleviated inflammation via facilitating microglia M2 polarization due to autophagy promotion, and inhibiting H3K9ac enrichment on promoter regions of TNF‑α and IL‑6.
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Copyright (c) 2022 Acta Neurobiologiae Experimentalis

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