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

期刊

BIOCHIMIE
卷 92, 期 6, 页码 707-715

出版社

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2010.02.008

关键词

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

资金

  1. National Institutes of Health [1F32KD084604-01, GM062887]
  2. GAANN fellowship [P200A070596]
  3. Institutional Training Grant [HL007260]
  4. VA Merit Award
  5. VAMC Research Excellence Award
  6. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007260] Funding Source: NIH RePORTER
  7. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM062887] Funding Source: NIH RePORTER

向作者/读者索取更多资源

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 SIP 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 interleukin 1-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 SIP 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.

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