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

Ashley J. Snider, K. Alexa Orr Gandy, Lina M. Obeid

Research output: Contribution to journalReview articlepeer-review

121 Scopus citations

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-α) and interleukin1-β (IL1-β). The activation of SK1 in this pathway has been shown to be, at least in part, required for mediating TNF-α and IL1-β 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.

Original languageEnglish (US)
Pages (from-to)707-715
Number of pages9
JournalBiochimie
Volume92
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • Ceramide
  • Inflammation
  • Sphingosine kinase
  • Sphingosine-1-phosphate
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Biochemistry

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