FTY720 Modulates Microglia Toward Anti-inflammatory Phenotype by Suppressing Autophagy via STAT1 Pathway.
Animals
Anti-Inflammatory Agents
/ pharmacology
Autophagy
/ drug effects
Cells, Cultured
Fingolimod Hydrochloride
/ pharmacology
Inflammation
/ pathology
Lipopolysaccharides
Mice, Inbred C57BL
Microglia
/ drug effects
Models, Biological
Phenotype
STAT1 Transcription Factor
/ metabolism
Signal Transduction
/ drug effects
Autophagy
FTY720
Microglia polarization
STAT1
Journal
Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
08
10
2019
accepted:
18
04
2020
pubmed:
29
4
2020
medline:
4
9
2021
entrez:
29
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32342246
doi: 10.1007/s10571-020-00856-9
pii: 10.1007/s10571-020-00856-9
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Lipopolysaccharides
0
STAT1 Transcription Factor
0
Fingolimod Hydrochloride
G926EC510T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-364Subventions
Organisme : National Natural Science Foundation of China
ID : 81571132
Organisme : National Natural Science Foundation of China
ID : 81873743
Organisme : National Natural Science Foundation of China
ID : 81801223
Organisme : Fundamental Research Funds for the Central Universities
ID : 2017KFYXJJ107
Organisme : Fundamental Research Funds for the Central Universities
ID : 2017KFYXJJ124
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