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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.

Background To explore the effect and mechanism of miR-16-5p on neuron apoptosis and inflammatory response induced by spinal cord injury (SCI). Methods Allen's weight-drop method and Basso Bcattie Bresnahan (BBB) rating scale were used to establish SCI rat model and assess locomotor function, respectively. Histopathology of SCI rats and Sham-operated rats was validated by hematoxylin and eosin (H&E) staining. After intravenous injection of miR-16-5p agomir, miR-16-5p antagomir, pcDNA3.1-Apelin-13 or negative controls into SCI rat tails, neuron apoptosis and the expression of miR-16-5p, Apelin-13, apoptotic proteins, inflammatory response-related proteins and ERK1/2 pathway-related protein were detected. Dual luciferase reporter gene assay was applied for identifying the binding between miR-16-5p and Apelin-13. Results SCI rats had locomotor impairment with markedly edema and hemorrhage. Upregulated miR-16-5p expression and downregulated Apelin-13 expression were presented in SCI rats. Intravenous injection of miR-16-5p antagomir or/and pcDNA3.1-Apelin-13 could increase the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1) and p-ERK1/2 expression while decrease the expression of pro-apoptotic proteins (cleaved caspase-3 and Bax) and inflammatory response-related proteins (TNF-α, IL-1β and IL-6). The reverse pattern was shown in rats injected with miR-16-5p agomir. MiR-16-5p targeted Apelin-13. Promotion of miR-16-5p agomir on SCI was attenuated by injection of agomir + pcDNA3.1-Apelin-13. Conclusions Downregulation of miR-16-5p could upregulate Apelin-13 expression to activate ERK1/2 pathway, thus alleviating SCI-induced neuron apoptosis and inflammatory response.