Sphingosine kinase and sphingosine-1-phosphate: regulators in autoimmune and inflammatory disease.

Sphingolipids and their metabolizing enzymes are beginning to be recognized as critical mediators in biological processes, specifically in inflammation and autoimmunity. Sphingosine kinases (SKs) and their lipid product sphingosine-1-phosphate (S1P) play essential roles in inflammatory signaling processes, as well as disease development and progression. SKs can be activated by numerous growth factors and cytokines, including TNF-α and IL-1β, leading to the generation of S1P. S1P exerts its biological effects on intracellular and extracellular targets, such as S1P receptors. In addition to roles in inflammatory signaling pathways SKs, S1P and S1P receptors have been implicated in immune cell function and trafficking, specifically in lymphocytes. This review will discuss the contribution of the bioactive sphingolipid S1P, its generating enzyme SK, and its cell surface receptors in the inflammatory and autoimmune diseases systemic lupus erythematosus, arthritis and inflammatory bowel disease.