Differential responses of human microglia and blood-derived myeloid cells to FTY720

被引：51

作者：

Durafourt, Bryce A. ^{[1
]}

Lambert, Caroline ^{[1
]}

Johnson, Trina A. ^{[1
]}

Blain, Manon ^{[1
]}

Bar-Or, Amit ^{[1
]}

Antel, Jack P. ^{[1
]}

机构：

[1] McGill Univ, Montreal Neurol Inst, Neuroimmunol Unit, Montreal, PQ H3A 2B4, Canada

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2011年 / 230卷 / 1-2期

关键词：

Human; Myeloid cells; Adult microglia; Multiple sclerosis; Fingolimod/FTY720; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RELAPSING MULTIPLE-SCLEROSIS; DENDRITIC CELLS; T-CELLS; IMMUNE-RESPONSES; ORAL FINGOLIMOD; SPHINGOSINE-1-PHOSPHATE; RECEPTORS; PHOSPHORYLATION;

D O I：

10.1016/j.jneuroim.2010.08.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Human microglia, monocyte-derived dendritic cells (DCs) and macrophages ex vivo express relatively higher levels of sphingosine-l-phosphate (SIP) receptor 1 (S1P1) mRNA as compared to other receptor subtypes. The S1P agonist FTY720 decreased ERK phosphorylation and induced myosin light chain (MLC) II phosphorylation only in macrophages and DCs. FTY720 inhibited IL-12p70 production (CD40L induced) by DCs and macrophages but not microglia (poly I:C induced). IL-10 production was increased in DCs and unaffected in other myeloid cells. Despite similar receptor expression patterns, the distinct myeloid cell populations present in the human CNS, under steady-state or inflammatory conditions, exhibit differential responses to FTY720. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：10 / 16

页数：7

共 42 条

[1] A new clinically relevant approach to expand myelin specific T cells [J].

Arbour, N ;

Lapointe, R ;

Saikali, P ;

McCrea, E ;

Regen, T ;

Antel, JP .

JOURNAL OF IMMUNOLOGICAL METHODS, 2006, 310 (1-2) :53-61

[2] CD40 engagement stimulates IL-12 p70 production by human microglial cells: basis for Th1 polarization in the CNS [J].

Becher, B ;

Blain, M ;

Antel, JP .

JOURNAL OF NEUROIMMUNOLOGY, 2000, 102 (01) :44-50

[3]

Beer MS, 2000, ANN NY ACAD SCI, V905, P118

[4] Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis [J].

Boven, LA ;

Van Meurs, M ;

Van Zwam, M ;

Wierenga-Wolf, A ;

Hintzen, RQ ;

Boot, RG ;

Aerts, JM ;

Amor, S ;

Nieuwenhuis, EE ;

Laman, JD .

BRAIN, 2006, 129 :517-526

[5] The immune modulator FTY720 targets sphingosine 1-phosphate receptors [J].

Brinkmann, V ;

Davis, MD ;

Heise, CE ;

Albert, R ;

Cottens, S ;

Hof, R ;

Bruns, C ;

Prieschl, E ;

Baumruker, T ;

Hiestand, P ;

Foster, CA ;

Zollinger, M ;

Lynch, KR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (24) :21453-21457

[6] FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system [J].

Brinkmann, Volker .

BRITISH JOURNAL OF PHARMACOLOGY, 2009, 158 (05) :1173-1182

[7] Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis [J].

Cohen, Jeffrey A. ;

Barkhof, Frederik ;

Comi, Giancarlo ;

Hartung, Hans-Peter ;

Khatri, Bhupendra O. ;

Montalban, Xavier ;

Pelletier, Jean ;

Capra, Ruggero ;

Gallo, Paolo ;

Izquierdo, Guillermo ;

Tiel-Wilck, Klaus ;

de Vera, Ana ;

Jin, James ;

Stites, Tracy ;

Wu, Stacy ;

Aradhye, Shreeram ;

Kappos, Ludwig .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (05) :402-415

[8] Brain sphingosine-1-phosphate receptors: Implication for FTY720 in the treatment of multiple sclerosis [J].

Dev, Kumlesh K. ;

Mullershausen, Florian ;

Mattes, Henri ;

Kuhn, Rainer R. ;

Bilbe, Graeme ;

Hoyer, Daniel ;

Mir, Anis .

PHARMACOLOGY & THERAPEUTICS, 2008, 117 (01) :77-93

[9]

DSOUZA S, 1995, J NEUROSCI, V15, P7293

[10]

Duong CQ, 2004, BBA-MOL CELL BIOL L, V1682, P112

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