Abstract
Sphingosine kinase (Sphk) has been shown to be activated by growth factor and survival factors, and one of its products, sphingosine-1-phosphate, plays an important role in the regulation of various cellular responses. However, the effect of Sphk on the maturation and immunostimulatory function of dendritic cells (DCs) still remains largely unknown. In this study, we examined whether sphingosine kinase inhibitor (SKI) can influence co-stimulatory molecules (CD40, CD80, CD86 and MHC class II) and cytokine production (IL-12 and IL-10) in murine bone marrow-derived DCs. SKI significantly inhibited co-stimulatory molecules in DCs. SKI suppressed IL-12 production by DCs and IFN-gamma production by T cells. In addition, SKI-inhibited LPS induced the translocation of nuclear factor-kappaB, whereas it did not affect the degradation of IL-1 receptor-associated kinase-1 by LPS. These novel findings provide new insight into the immunopharmacological role of SKI in terms of its effects on DCs. These findings open a possibility for further understanding of the immunopharmacological functions of SKI, as well as therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / metabolism
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Apoptosis / drug effects
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / immunology
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Cell Aggregation / drug effects
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Cell Aggregation / immunology
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Cells, Cultured
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Coculture Techniques
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Enzyme Inhibitors / pharmacology*
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Flow Cytometry
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Interleukin-10 / metabolism
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Interleukin-12 / metabolism
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Lipopolysaccharides / pharmacology
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Lysophospholipids / pharmacology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mutation
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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RNA, Small Interfering / genetics
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Receptors, Lysosphingolipid / antagonists & inhibitors
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Receptors, Lysosphingolipid / metabolism
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Sphingosine / analogs & derivatives
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Sphingosine / pharmacology
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Th1 Cells / cytology
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Th1 Cells / drug effects
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Th1 Cells / immunology*
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Transcription Factor RelA / metabolism
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Transfection
Substances
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Antigens, CD
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Enzyme Inhibitors
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Lipopolysaccharides
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Lysophospholipids
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RNA, Small Interfering
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Receptors, Lysosphingolipid
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Transcription Factor RelA
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Interleukin-10
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Interleukin-12
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sphingosine 1-phosphate
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Phosphotransferases (Alcohol Group Acceptor)
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sphingosine kinase
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Sphingosine