Abstract
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.
Copyright © 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cytokines / biosynthesis
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Enzyme-Linked Immunosorbent Assay
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Fingolimod Hydrochloride
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Gene Expression
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Humans
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Immunosuppressive Agents / pharmacology*
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Lysophospholipids / immunology
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Lysophospholipids / metabolism
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Macrophages / drug effects
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Macrophages / immunology
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Macrophages / metabolism
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Microglia / drug effects*
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Microglia / immunology
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Microglia / metabolism
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Myeloid Cells / drug effects*
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Myeloid Cells / immunology
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Myeloid Cells / metabolism
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Propylene Glycols / pharmacology*
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RNA, Messenger / analysis
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Receptors, Lysosphingolipid / drug effects
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Receptors, Lysosphingolipid / immunology
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Receptors, Lysosphingolipid / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sphingosine / analogs & derivatives*
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Sphingosine / immunology
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Sphingosine / metabolism
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Sphingosine / pharmacology
Substances
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Cytokines
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Immunosuppressive Agents
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Lysophospholipids
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Propylene Glycols
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RNA, Messenger
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Receptors, Lysosphingolipid
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sphingosine 1-phosphate
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Fingolimod Hydrochloride
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Sphingosine