Snider Ashley J
Northport Veterans Affairs Medical Center, Northport, NY 11768, USA and Department of Medicine, Stony Brook University, 100 Nicolls Road, Health Sciences Center L15-023, Stony Brook, NY 11794, USA.
Int J Clin Rheumtol. 2013 Aug 1;8(4). doi: 10.2217/ijr.13.40.
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.
鞘脂及其代谢酶开始被认为是生物过程中的关键介质，特别是在炎症和自身免疫方面。鞘氨醇激酶（SKs）及其脂质产物鞘氨醇-1-磷酸（S1P）在炎症信号传导过程以及疾病的发生和发展中起着重要作用。SKs可被多种生长因子和细胞因子激活，包括TNF-α和IL-1β，从而导致S1P的生成。S1P对细胞内和细胞外靶点发挥其生物学作用，如S1P受体。除了在炎症信号通路中的作用外，SKs、S1P和S1P受体还与免疫细胞功能和运输有关，特别是在淋巴细胞中。本综述将讨论生物活性鞘脂S1P、其生成酶SK及其细胞表面受体在炎症和自身免疫性疾病系统性红斑狼疮、关节炎和炎症性肠病中的作用。
