FTY720 Modulates Microglia Toward Anti-inflammatory Phenotype by Suppressing Autophagy via STAT1 Pathway (original ) (raw )
Araya J et al (2019) PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis. Autophagy 15:510–526. https://doi.org/10.1080/15548627.2018.1532259 Article CAS PubMed Google Scholar
Biswas SK, Mantovani A (2010) Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 11:889–896. https://doi.org/10.1038/ni.1937 Article CAS PubMed Google Scholar
Blanc CA, Rosen H, Lane TE (2014) FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination. J Neuroinflamm 11:138. https://doi.org/10.1186/s12974-014-0138-y Article CAS Google Scholar
Boche D, Perry VH, Nicoll JA (2013) Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol 39:3–18. https://doi.org/10.1111/nan.12011 Article CAS PubMed Google Scholar
Brinkmann V et al (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9:883–897. https://doi.org/10.1038/nrd3248 Article CAS PubMed Google Scholar
Cadwell K (2016) Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis. Nat Rev Immunol 16:661–675. https://doi.org/10.1038/nri.2016.100 Article CAS PubMed PubMed Central Google Scholar
Carta AR, Pisanu A (2013) Modulating microglia activity with PPAR-gamma agonists: a promising therapy for Parkinson's disease? Neurotoxicol Res 23:112–123. https://doi.org/10.1007/s12640-012-9342-7 Article CAS Google Scholar
Chang CP, Su YC, Lee PH, Lei HY (2013) Targeting NFKB by autophagy to polarize hepatoma-associated macrophage differentiation. Autophagy 9:619–621. https://doi.org/10.4161/auto.23546 Article CAS PubMed PubMed Central Google Scholar
Chen ZH et al (2016) Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium. Autophagy 12:297–311. https://doi.org/10.1080/15548627.2015.1124224 Article CAS PubMed Google Scholar
Chhor V et al (2013) Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain Behav Immunity 32:70–85. https://doi.org/10.1016/j.bbi.2013.02.005 Article CAS Google Scholar
Cipriani R, Chara JC, Rodriguez-Antiguedad A, Matute C (2015) FTY720 attenuates excitotoxicity and neuroinflammation. J Neuroinflamm 12:86. https://doi.org/10.1186/s12974-015-0308-6 Article Google Scholar
Cui L, Li C, Gao G, Zhuo Y, Yang L, Cui N, Zhang S (2019a) FTY720 inhibits the activation of pancreatic stellate cells by promoting apoptosis and suppressing autophagy via the AMPK/mTOR pathway. Life Sci 217:243–250. https://doi.org/10.1016/j.lfs.2018.12.019 Article CAS PubMed Google Scholar
Dai J, Zhang X, Li L, Chen H, Chai Y (2017) Autophagy inhibition contributes to ROS-producing NLRP3-dependent inflammasome activation and cytokine secretion in high glucose-induced macrophages. Cell Physiol Biochem 43:247–256. https://doi.org/10.1159/000480367 Article CAS PubMed Google Scholar
Das A et al (2016) Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia. J Neuroinflamm 13:182. https://doi.org/10.1186/s12974-016-0644-1 Article CAS Google Scholar
Das A, Arifuzzaman S, Kim SH, Lee YS, Jung KH, Chai YG (2017) FTY720 (fingolimod) regulates key target genes essential for inflammation in microglial cells as defined by high-resolution mRNA sequencing. Neuropharmacology 119:1–14. https://doi.org/10.1016/j.neuropharm.2017.03.034 Article CAS PubMed Google Scholar
Fu Y et al (2014) Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study. JAMA Neurol 71:1092–1101. https://doi.org/10.1001/jamaneurol.2014.1065 Article PubMed Google Scholar
Fu Y, Liu Q, Anrather J, Shi FD (2015) Immune interventions in stroke. Nat Rev Neurol 11:524–535. https://doi.org/10.1038/nrneurol.2015.144 Article CAS PubMed PubMed Central Google Scholar
Hu X et al (2012) Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke 43:3063–3070. https://doi.org/10.1161/strokeaha.112.659656 Article CAS PubMed Google Scholar
Hu X et al (2014) Neurobiology of microglial action in CNS injuries: receptor-mediated signaling mechanisms and functional roles. Prog Neurobiol 119–120:60–84. https://doi.org/10.1016/j.pneurobio.2014.06.002 Article CAS PubMed Google Scholar
Hughes R et al (2018) Oral fingolimod for chronic inflammatory demyelinating polyradiculoneuropathy (FORCIDP trial): a double-blind, multicentre, randomised controlled trial. Lancet Neurol 17:689–698. https://doi.org/10.1016/s1474-4422(18)30202-3 Article CAS PubMed Google Scholar
Jiang P, Mizushima N (2015) LC3- and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells. Methods (San Diego, Calif) 75:13–18. https://doi.org/10.1016/j.ymeth.2014.11.021 Article CAS Google Scholar
Kim KH, Lee MS (2014) Autophagy—a key player in cellular and body metabolism. Nat Rev Endocrinol 10:322–337. https://doi.org/10.1038/nrendo.2014.35 Article CAS PubMed Google Scholar
Lee JW et al (2019) TLR4 (toll-like receptor 4) activation suppresses autophagy through inhibition of FOXO3 and impairs phagocytic capacity of microglia. Autophagy 15:753–770. https://doi.org/10.1080/15548627.2018.1556946 Article CAS PubMed Google Scholar
Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27–42. https://doi.org/10.1016/j.cell.2007.12.018 Article CAS PubMed PubMed Central Google Scholar
Li J, Kim SG, Blenis J (2014) Rapamycin: one drug, many effects. Cell Metab 19:373–379. https://doi.org/10.1016/j.cmet.2014.01.001 Article CAS PubMed PubMed Central Google Scholar
Li X, Wang M-H, Qin C, Fan W-H, Tian D-S, Liu J-L (2017) Fingolimod suppresses neuronal autophagy through the mTOR/p70S6K pathway and alleviates ischemic brain damage in mice. PLoS ONE. https://doi.org/10.1371/journal.pone.0188748 Article PubMed PubMed Central Google Scholar
Mecha M, Feliu A, Carrillo-Salinas FJ, Rueda-Zubiaurre A, Ortega-Gutierrez S, de Sola RG, Guaza C (2015) Endocannabinoids drive the acquisition of an alternative phenotype in microglia. Brain Behav Immun 49:233–245. https://doi.org/10.1016/j.bbi.2015.06.002 Article CAS PubMed Google Scholar
Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell 140:313–326. https://doi.org/10.1016/j.cell.2010.01.028 Article CAS PubMed PubMed Central Google Scholar
Nazio F et al (2013) mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol 15:406–416. https://doi.org/10.1038/ncb2708 Article CAS PubMed Google Scholar
Neumann H, Kotter MR, Franklin RJ (2009) Debris clearance by microglia: an essential link between degeneration and regeneration. Brain 132:288–295. https://doi.org/10.1093/brain/awn109 Article CAS PubMed Google Scholar
Noda H, Takeuchi H, Mizuno T, Suzumura A (2013) Fingolimod phosphate promotes the neuroprotective effects of microglia. J Neuroimmunol 256:13–18. https://doi.org/10.1016/j.jneuroim.2012.12.005 Article CAS PubMed Google Scholar
Patel AR, Ritzel R, McCullough LD, Liu F (2013) Microglia and ischemic stroke: a double-edged sword. Int J Physiol Pathophysiol Pharmacol 5:73–90PubMed PubMed Central Google Scholar
Pratt J, Annabi B (2014) Induction of autophagy biomarker BNIP3 requires a JAK2/STAT3 and MT1-MMP signaling interplay in Concanavalin-A-activated U87 glioblastoma cells. Cell Signal 26:917–924. https://doi.org/10.1016/j.cellsig.2014.01.012 Article CAS PubMed Google Scholar
Qin C et al (2017) Fingolimod protects against ischemic white matter damage by modulating microglia toward M2 polarization via STAT3 pathway. Stroke 48:3336–3346. https://doi.org/10.1161/strokeaha.117.018505 Article CAS PubMed PubMed Central Google Scholar
Qin C et al (2018) Microglial TLR4-dependent autophagy induces ischemic white matter damage via STAT1/6 pathway. Theranostics 8:5434–5451. https://doi.org/10.7150/thno.27882 Article CAS PubMed PubMed Central Google Scholar
Rothhammer V et al (2017) Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation. Proc Natl Acad Sci USA 114:2012–2017. https://doi.org/10.1073/pnas.1615413114 Article CAS PubMed Google Scholar
Saijo K, Glass CK (2011) Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol 11:775–787. https://doi.org/10.1038/nri3086 Article CAS PubMed Google Scholar
Shi H, Wang J, Wang J, Huang Z, Yang Z (2018) IL-17A induces autophagy and promotes microglial neuroinflammation through ATG5 and ATG7 in intracerebral hemorrhage. J Neuroimmunol 323:143–151. https://doi.org/10.1016/j.jneuroim.2017.07.015 Article CAS PubMed Google Scholar
Su P, Zhang J, Wang D, Zhao F, Cao Z, Aschner M, Luo W (2016) The role of autophagy in modulation of neuroinflammation in microglia. Neuroscience 319:155–167. https://doi.org/10.1016/j.neuroscience.2016.01.035 Article CAS PubMed Google Scholar
Varnum MM, Ikezu T (2012) The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's disease brain. Arch Immunol et Ther Exp 60:251–266. https://doi.org/10.1007/s00005-012-0181-2 Article CAS Google Scholar
Wang XL, Qiao CM, Liu JO, Li CY (2017) Inhibition of the SOCS1-JAK2-STAT3 signaling pathway confers neuroprotection in rats with ischemic stroke. Cell Physiol Biochem 44:85–98. https://doi.org/10.1159/000484585 Article PubMed Google Scholar
Wei Y et al (2011) Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol 69:119–129. https://doi.org/10.1002/ana.22186 Article CAS PubMed Google Scholar
Yang D et al (2014a) Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns. J Neurosci 34:16467–16481. https://doi.org/10.1523/JNEUROSCI.2582-14.2014 Article PubMed PubMed Central Google Scholar
Yang Z, Zhang N, Shen H, Lin C, Lin L, Yuan B (2014b) Microglial activation with reduction in autophagy limits white matter lesions and improves cognitive defects during cerebral hypoperfusion. Curr Neurovasc Res 11:223–229Article CAS Google Scholar
Yang Z et al (2015a) Toll-like receptor-4-mediated autophagy contributes to microglial activation and inflammatory injury in mouse models of intracerebral haemorrhage. Neuropathol Appl Neurobiol 41:e95–106. https://doi.org/10.1111/nan.12177 Article CAS PubMed Google Scholar
Yang Z, Zhong L, Zhong S, Xian R, Yuan B (2015b) Hypoxia induces microglia autophagy and neural inflammation injury in focal cerebral ischemia model. Exp Mol Pathol 98:219–224. https://doi.org/10.1016/j.yexmp.2015.02.003 Article CAS PubMed Google Scholar
Yenari MA, Kauppinen TM, Swanson RA (2010) Microglial activation in stroke: therapeutic targets. Neurotherapeutics 7:378–391. https://doi.org/10.1016/j.nurt.2010.07.005 Article CAS PubMed PubMed Central Google Scholar
Yorimitsu T, Klionsky DJ (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ 12(Suppl 2):1542–1552. https://doi.org/10.1038/sj.cdd.4401765 Article CAS PubMed PubMed Central Google Scholar
Yu Z, Sun D (2015) MSX3 switches microglia polarization and protects from inflammation-induced. Demyelination 35:6350–6365. https://doi.org/10.1523/jneurosci.2468-14.2015 Article CAS Google Scholar
Zhang SQ, Ding FF, Liu Q, Tian YY, Wang W, Qin C (2019) Autophagy inhibition exerts neuroprotection on white matter ischemic damage after chronic cerebral hypoperfusion in mice. Brain Res 1721:146337. https://doi.org/10.1016/j.brainres.2019.146337 Article CAS PubMed Google Scholar
Zhu Z et al (2015) Combination of the immune modulator fingolimod with alteplase in acute ischemic stroke: a pilot trial. Circulation 132:1104–1112. https://doi.org/10.1161/CIRCULATIONAHA.115.016371 Article CAS PubMed PubMed Central Google Scholar