Sphingosine kinase inhibitor suppresses a Th1 polarization via the inhibition of immunostimulatory activity in murine bone marrow-derived dendritic cells.
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.
Jung
In Duk
ID
Department of Microbiology and Immunology, National Research Laboratory of Dendritic Cell Differentiation and Regulation, Medical Research Institute, College of Medicine, Pusan National University, Ami-dong 1-10, Seo-gu, Busan 602-739, Korea.
Lee
Jun Sik
JS
Kim
Yong Joo
YJ
Jeong
Young-Il
YI
Lee
Chang-Min
CM
Baumruker
Thomas
T
Billlich
Andreas
A
Banno
Yoshiko
Y
Lee
Min Goo
MG
Ahn
Soon-Choel
SC
Park
Won Sun
WS
Han
Jin
J
Park
Yeong-Min
YM
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D000099157:Sphingosine Kinase
D015703:Antigens, CD; D004791:Enzyme Inhibitors; D016753:Interleukin-10; D018664:Interleukin-12; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D051996:Transcription Factor RelA; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate