TY - JOUR
T1 - Sphingosine kinase
T2 - Role in regulation of bioactive sphingolipid mediators in inflammation
AU - Snider, Ashley J.
AU - Alexa Orr Gandy, K.
AU - Obeid, Lina M.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants 1F32KD084604-01 (AJS), GM062887 (LMO), and GAANN fellowship P200A070596 and Institutional Training Grant, HL007260 (KAOG). As well as, VA Merit Award (LMO) and by the VAMC Research Excellence Award Program (REAP) (LMO and AJS). We would like to thank Kathy Wiita-Fisk for her administrative assistance.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - Ceramide
KW - Inflammation
KW - Sphingosine kinase
KW - Sphingosine-1-phosphate
KW - Tumor necrosis factor-alpha
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U2 - 10.1016/j.biochi.2010.02.008
DO - 10.1016/j.biochi.2010.02.008
M3 - Review article
C2 - 20156522
AN - SCOPUS:77953293446
SN - 0300-9084
VL - 92
SP - 707
EP - 715
JO - Biochimie
JF - Biochimie
IS - 6
ER -