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Biochimie. 2010 Jun;92(6):707-15. doi: 10.1016/j.biochi.2010.02.008. Epub 2010 Feb 13.

Sphingosine kinase: Role in regulation of bioactive sphingolipid mediators in inflammation.

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  • 1Department of Medicine, Medical University of South Carolina, Charleston, SC 29403, USA.

Abstract

Sphingolipids and their synthetic enzymes are emerging as important mediators in inflammatory responses and as regulators of immune cell functions. In particular, sphingosine kinase (SK) and its product sphingosine-1-phosphate (S1P) have been extensively implicated in these processes. SK catalyzes the phosphorylation of sphingosine to S1P and exists as two isoforms, SK1 and SK2. SK1 has been shown to be activated by cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin1-beta (IL1-beta). The activation of SK1 in this pathway has been shown to be, at least in part, required for mediating TNF-alpha and IL1-beta inflammatory responses in cells, including induction of cyclo-oxygenase 2 (COX2). In addition to their role in inflammatory signaling, SK and S1P have also been implicated in various immune cell functions including, mast cell degranulation, migration of neutrophils, and migration and maturation of lymphocytes. The involvement of sphingolipids and sphingolipid metabolizing enzymes in inflammatory signaling and immune cell functions has implicated these mediators in numerous inflammatory disease states as well. The contribution of these mediators, specifically SK1 and S1P, to inflammation and disease are discussed in this review.

Published by Elsevier Masson SAS.

PMID:
20156522
[PubMed - indexed for MEDLINE]
PMCID:
PMC2878898
Free PMC Article
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