Sphingosine kinase inhibitor suppresses a Th1 polarization via the inhibition of immunostimulatory activity in murine bone marrow-derived dendritic cells

In Duk Jung, Jun Sik Lee, Yong Joo Kim, Young Il Jeong, Chang Min Lee, Thomas Baumruker, Andreas Billlich, Yoshiko Banno, Min-Goo Lee, Soon Choel Ahn, Won Sun Park, Jin Han, Yeong Min Park

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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-γ production by T cells. In addition, SKI-inhibited LPS induced the translocation of nuclear factor-κB, 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.

Original languageEnglish
Pages (from-to)411-426
Number of pages16
JournalInternational Immunology
Volume19
Issue number4
DOIs
Publication statusPublished - 2007 Apr 1

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ASJC Scopus subject areas

  • Immunology

Cite this

Jung, I. D., Lee, J. S., Kim, Y. J., Jeong, Y. I., Lee, C. M., Baumruker, T., Billlich, A., Banno, Y., Lee, M-G., Ahn, S. C., Park, W. S., Han, J., & Park, Y. M. (2007). Sphingosine kinase inhibitor suppresses a Th1 polarization via the inhibition of immunostimulatory activity in murine bone marrow-derived dendritic cells. International Immunology, 19(4), 411-426. https://doi.org/10.1093/intimm/dxm006