Edwards Laura J, Constantinescu Cris S
Division of Clinical Neurology, University of Nottingham, B Floor, Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Inflamm Allergy Drug Targets. 2009 Jul;8(3):182-90. doi: 10.2174/187152809788681010.
Platelet activating factor (PAF) is a phospholipid mediator of inflammation that is released early in inflammation by a variety of cell types. PAF acts largely by binding to its receptor, PAF-R, a G-protein coupled receptor found on a variety of cells, including cells of the immune system. PAF has been implicated in the pathogenesis of asthma and allergic conditions, but its role in autoimmune conditions has been less extensively investigated. Here, we review the accumulating evidence for the role of PAF/PAF-R pathway in autoimmune diseases. We describe studies showing up-regulation of PAF-R in inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis and review the evidence from the use of PAF-R antagonists. We describe results of experimental models of inflammatory diseases that point to a role for PAF/PAF-R pathway including those using PAF-R antagonists and those employing PAF-R knockout mice and knockout mice for cytosolic phospholipase2. Recent experiments from our laboratory show that PAF/PAF-R pathway may influence T cell responses and favour the Th17 phenotype (in which T cells produce tissue destructive proinflammatory cytokine IL-17). The PAF/PAF-R pathway is a promising target for pharmacological intervention in autoimmune diseases.
血小板活化因子（PAF）是一种炎症的磷脂介质，在炎症早期由多种细胞类型释放。PAF主要通过与其受体PAF-R结合发挥作用，PAF-R是一种G蛋白偶联受体，存在于包括免疫系统细胞在内的多种细胞上。PAF与哮喘和过敏性疾病的发病机制有关，但其在自身免疫性疾病中的作用研究较少。在此，我们综述了PAF/PAF-R途径在自身免疫性疾病中作用的越来越多的证据。我们描述了显示PAF-R在炎症性肠病、类风湿性关节炎和多发性硬化症中上调的研究，并综述了使用PAF-R拮抗剂的证据。我们描述了炎症性疾病实验模型的结果，这些结果表明PAF/PAF-R途径发挥作用，包括使用PAF-R拮抗剂的模型以及使用PAF-R基因敲除小鼠和胞质磷脂酶2基因敲除小鼠的模型。我们实验室最近的实验表明，PAF/PAF-R途径可能影响T细胞反应，并有利于Th17表型（其中T细胞产生组织破坏性促炎细胞因子IL-17）。PAF/PAF-R途径是自身免疫性疾病药物干预的一个有前景的靶点。
