Apelin-13 regulates LPS-induced N9 microglia polarization involving STAT3 signaling pathway

The process of neurodegenerative diseases has always been accompanied by neuroinflammatory response characterized by microglia activation. Two phenotypes of microglial polarization: the classically activated M1 type and the alternative activated M2 type, have been described. Although apelin-13 has been shown to have neuroprotective effects, its specific mechanism of anti-neuritis is still unclear. The aim of this study was to investigate whether apelin-13 can exert anti-neuroinflammatory effects by regulating the polarization of N9 microglia. MTT assay showed that 0.1 AM apelin-13 (24 h) and 2 mu g/mL LPS (6 h) treatment had no significant effect on cell viability of N9 microglia. The combined treatment of Apelin-13 and LPS did not affect the viability of N9 microglia. N9 microglia were pretreated with 0.1 mu M apelin-13 for 24 h, followed by incubation with LPS for 6 h. Morphological results indicated that apelin-13 (0.1 mu M) inhibited LPS-induced N9 microglial activation as observed by smaller soma and slender process compared to LPS-treated group. Western blot confirmed that apelin-13 decreased the level of proinflammatory factor iNOS, IL-6 and up-regulated the level of anti-inflammatory factor arg-1 and IL 10 in N9 microglia. Flow cytometry revealed that apelin-13 inhibited the expression of M1 microglia activation marker CD86 and up-regulated the expression of M2 marker CD206. Furthermore, the data displayed that apelin-13 decreased the expression of p-STAT3 and the radio of p-STAT3/t-STAT3 in M1-type N9 microglia induced by LPS. In conclusion, our results indicated apelin-13 ameliorated neuroinflammation by shifting N9 microglial M1 polarization toward the M2 phenotype, the underlying mechanism of which may be related to STAT3 signals.