Sphingosine 1-phosphate, a key mediator of the cytokine network: Juxtacrine signaling

Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite, which has emerged as an important signaling mediator participating in the regulation of multiple cellular processes. The discovery of a family of SIP receptors, together with the more recently identified intracellular targets, has provided fundamental understanding of the multi-faceted actions of SIP. Evidence from both in vitro and in vivo studies has implicated the SIP signaling system in the control of immunity, inflammation and many associated diseases. Enigmatically, SIP appears to have both pro- and anti-inflammatory effects depending on the cell context. Here, we review this emerging area and argue for a pivotal role for SIP, as a key mediator of the cytokine network, acting through juxtacrine signaling in the immune system. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.