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首页> 外文期刊>Cellular Physiology and Biochemistry >Targeting Sphingosine 1-phosphate (S1P) Levels and S1P Receptor Functions for Therapeutic Immune Interventions
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Targeting Sphingosine 1-phosphate (S1P) Levels and S1P Receptor Functions for Therapeutic Immune Interventions

机译：靶向鞘氨醇1-磷酸（S1P）的水平和S1P受体功能的治疗性免疫干预

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摘要

Sphingosine 1-phosphate (S1P) is an important regulator of many different immune functions including lymphocyte circulation, antigen presentation, and T cell development. It stimulates five G protein-coupled receptors designated S1Psub1-5/sub, which are also expressed by immune cells. S1P receptors couple to different heterotrimeric G proteins including G alpha i, q, and 12/13, and elicit cellular signalling events by activating the small GTPases Rac and Rho and protein kinases Akt, ERK, and JNK, and by inducing cellular calcium flux and inhibiting cAMP accumulation, amongst others. S1P is the exit signal for lymphocytes leaving lymphoid organs and present in blood and lymph at high nanomolar concentrations due to the S1P-producing activity of sphingosine kinases (SK). The S1P-degrading enzyme S1P-lyase maintains low amounts of S1P in lymphoid organs. Disrupting this concentration difference by S1P receptor agonists and antagonists like FTY720, SEW2871, and VPC23019, by an anti-S1P antibody, or by inhibiting the S1P-lyase has therapeutic potential for autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis and for many other disorders like cancer, fibrosis, inflammation, macular degeneration, diabetic retinopathy, and glaucoma. This report aims to provide a brief overview of concepts, approaches, pharmaceutical compounds, and targets that are currently used to modulate S1P-driven immune functions.
机译：1-磷酸鞘氨醇（S1P）是许多不同免疫功能的重要调节剂，包括淋巴细胞循环，抗原呈递和T细胞发育。它刺激五种G蛋白偶联受体，称为S1P 1-5 ，它们也由免疫细胞表达。 S1P受体与不同的异源三聚体G蛋白偶联，包括G alpha i，q和12/13，并通过激活小的GTPases Rac和Rho以及蛋白激酶Akt，ERK和JNK，并诱导细胞钙通量和抑制cAMP积累等。 S1P是淋巴细胞离开淋巴器官的出口信号，由于鞘氨醇激酶（SK）的S1P产生活性，其以高纳摩尔浓度存在于血液和淋巴液中。 S1P降解酶S1P裂解酶在淋巴器官中维持少量的S1P。通过S1P受体激动剂和拮抗剂（例如FTY720，SEW2871和VPC23019），抗S1P抗体或通过抑制S1P裂解酶来破坏这种浓度差异，具有治疗自身免疫性疾病（如多发性硬化症（MS）和类风湿性关节炎以及许多其他疾病）的潜力其他疾病，例如癌症，纤维化，炎症，黄斑变性，糖尿病性视网膜病和青光眼。本报告旨在简要概述当前用于调节S1P驱动的免疫功能的概念，方法，药物化合物和靶标。

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