International Immunology Advance Access originally published online on February 16, 2007
International Immunology 2007 19(4):411-426; doi:10.1093/intimm/dxm006
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Sphingosine kinase inhibitor suppresses a Th1 polarization via the inhibition of immunostimulatory activity in murine bone marrow-derived dendritic cells
1 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
2 Department of Pharmacy, College of Pharmacy, Pusan National University, Geumjeong-gu, Busan 602-735, Korea
3 Department of Microbiology, College of Natural Science, Pusan National University, Geumjeong-gu, Busan 609-735, Korea
4 Novartis Institutes for BioMedical Research, Brunnerstrasse 59, Vienna A-1235, Austria
5 Department of Cell Signaling, Graduate School of Medicine, Gifu University, Japan
6 Department of Physiology, College of Medicine, Korea University, Seoul 136-705, Korea
7 Mitochondria Signaling Laboratory, FIRST project group, Department of Physiology and Biophysics, College of Medicine, Inje University, Gaegeum-dong, Busnajin-Gu, Busan 614-735, Korea
Correspondence to: Y.-M. Park; E-mail: immunpym{at}pusan.ac.kr
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-
production by T cells. In addition, SKI-inhibited LPS induced the translocation of nuclear factor-
B, 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.
Keywords: dendritic cell, sphingosine kinase, sphingosine-1-phosphate, Th1 polarization
Transmitting editor: K. Inaba
Received 30 November 2006, accepted 16 January 2007.
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