Differential responses of human microglia and blood-derived myeloid cells to FTY720.
Human microglia, monocyte-derived dendritic cells (DCs) and macrophages ex vivo express relatively higher levels of sphingosine-1-phosphate (S1P) 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.
Durafourt
Bryce A
BA
Neuroimmunology Unit, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada.
Lambert
Caroline
C
Johnson
Trina A
TA
Blain
Manon
M
Bar-Or
Amit
A
Antel
Jack P
JP
D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000068876:Fingolimod Hydrochloride; D015870:Gene Expression; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008246:Lysophospholipids / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011409:Propylene Glycols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D049349:Receptors, Lysosphingolipid / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D011409:Propylene Glycols; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine