Sphingosine-1-phosphate inhibits the cytotoxic activity of NK cells via Gs protein-mediated signalling

  • Authors:
    • Mariana Lagadari
    • Katja Lehmann
    • Mirjana Ziemer
    • Krisztina Truta-Feles
    • Luciana Berod
    • Marco Idzko
    • Dagmar Barz
    • Thomas Kamradt
    • Azzam A. Maghazachi
    • Johannes Norgauer
  • Corresponding author:
  • View Affiliations

  • Published online on: Thursday, January 1, 2009
  • Pages: 287-294 DOI: 10.3892/ijo_00000151

Abstract

Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that transmits signals through G-protein-coupled receptors to control cellular differentiation, survival, and several functions of immune cells. S1P is a chemoattractant for NK cells, which are critical members of the immunological tumor surveillance machinery. In this study we analyzed the influence of S1P on the interaction of NK cells with tumor cells such as the human melanoma cell line Hs294T and the Burkitt's lymphoma cell line Raji. We found that S1P inhibited the cytotoxic activity of NK cells. Analysis of signal transduction pathways revealed that S1P induced common signalling pathways of chemotaxins such as Gi protein-dependent actin reorganization and activation of the phosphatidylinositol 3-kinase (PI3K) dependent signal molecules, protein kinase B (PKB/Akt) and glycogen synthase kinase-3β (GSK-3β). In contrast to most chemotaxins, S1P is also able to activate Gs-dependent signalling molecules. This signalling cascade involves increase of cAMP levels and protein kinase A (PKA) activation. Additionally, blocking the regulatory subunits of PKA I abrogated the inhibitory effect of S1P, whereas the catalytic subunits were not involved. Our data indicate that S1P may contributes to the tumor escape from NK cell-dependent immunological surveillance machinery.
Journal Cover

January 2009
Volume 34 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
2014 I.F. (Expected) ≥ 3.258 Ranked #30/202 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Lagadari, M., Lehmann, K., Ziemer, M., Truta-Feles, K., Berod, L., Idzko, M. ... Norgauer, J. (2009). Sphingosine-1-phosphate inhibits the cytotoxic activity of NK cells via Gs protein-mediated signalling. International Journal of Oncology, 34, 287-294. http://dx.doi.org/10.3892/ijo_00000151
MLA
Lagadari, M., Lehmann, K., Ziemer, M., Truta-Feles, K., Berod, L., Idzko, M., Barz, D., Kamradt, T., Maghazachi, A. A., Norgauer, J."Sphingosine-1-phosphate inhibits the cytotoxic activity of NK cells via Gs protein-mediated signalling". International Journal of Oncology 34.1 (2009): 287-294.
Chicago
Lagadari, M., Lehmann, K., Ziemer, M., Truta-Feles, K., Berod, L., Idzko, M., Barz, D., Kamradt, T., Maghazachi, A. A., Norgauer, J."Sphingosine-1-phosphate inhibits the cytotoxic activity of NK cells via Gs protein-mediated signalling". International Journal of Oncology 34, no. 1 (2009): 287-294. http://dx.doi.org/10.3892/ijo_00000151