FTY720 Modulates Microglia Toward Anti-inflammatory Phenotype by Suppressing Autophagy via STAT1 Pathway

Zi Wei Hu, Luo Qi Zhou, Sheng Yang, Man Chen, Hai Han Yu, Ran Tao, Long Jun Wu, Wei Wang, Qiang Zhang, Chuan Qin, Dai Shi Tian

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Since microglia-associated neuroinflammation plays a pivotal role in the progression of white matter diseases, modulating microglial activation has been suggested as a potential therapeutic strategy. Here, we investigated the anti-inflammatory effects of fingolimod (FTY720) on microglia and analyzed the crosstalk between microglia autophagy and neuroinflammation. Lipopolysaccharide (LPS)-induced primary cultured microglia model was established. Microglial phenotypes were assessed by Western blot, quantitative real-time polymerase chain reaction (RT-PCR) and flow cytometry. Autophagy was evaluated by immunofluorescence, MDC staining and Western blot. Rapamycin was used to investigate the role of autophagic process in regulating microglial phenotypes. The signaling markers were screened by RT-PCR and Western blot. FTY720 shifted microglial phenotype from pro-inflammatory state to anti-inflammatory state and inhibited microglial autophagy under lipopolysaccharide (LPS) treatment. Rapamycin reversed the effect of FTY720 on phenotype transformation of microglia. The results of mechanism studies have shown that FTY720 notably repressed LPS-induced STAT1 activity, which was reactivated by rapamycin. Our research suggested that FTY720 could significantly transform pro-inflammatory microglia into anti-inflammatory microglia by suppressing autophagy via STAT1.

Original languageEnglish (US)
JournalCellular and molecular neurobiology
DOIs
StateAccepted/In press - 2020

Keywords

  • Autophagy
  • FTY720
  • Microglia polarization
  • STAT1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Hu, Z. W., Zhou, L. Q., Yang, S., Chen, M., Yu, H. H., Tao, R., Wu, L. J., Wang, W., Zhang, Q., Qin, C., & Tian, D. S. (Accepted/In press). FTY720 Modulates Microglia Toward Anti-inflammatory Phenotype by Suppressing Autophagy via STAT1 Pathway. Cellular and molecular neurobiology. https://doi.org/10.1007/s10571-020-00856-9