Department of Medicine, Medical University of South Carolina, Charleston, SC 29403, USA.
Biochimie. 2010 Jun;92(6):707-15. doi: 10.1016/j.biochi.2010.02.008. Epub 2010 Feb 13.
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.
鞘脂及其合成酶作为炎症反应的重要介质和免疫细胞功能的调节剂而逐渐受到关注。特别是，鞘氨醇激酶（SK）及其产物 1-磷酸鞘氨醇（S1P）已广泛涉及这些过程。SK 催化鞘氨醇磷酸化为 S1P，存在两种同工酶，SK1 和 SK2。已有研究表明，细胞因子如肿瘤坏死因子-α（TNF-α）和白细胞介素 1-β（IL1-β）可激活 SK1。该途径中 SK1 的激活至少部分是介导 TNF-α和 IL1-β细胞炎症反应所必需的，包括诱导环氧化酶 2（COX2）。除了在炎症信号转导中的作用外，SK 和 S1P 还与各种免疫细胞功能有关，包括肥大细胞脱颗粒、中性粒细胞迁移以及淋巴细胞的迁移和成熟。鞘脂和鞘脂代谢酶在炎症信号转导和免疫细胞功能中的参与表明这些介质在许多炎症疾病状态中也有涉及。本综述讨论了这些介质，特别是 SK1 和 S1P，在炎症和疾病中的作用。
