Prostanoids in immunity: Roles revealed by mice deficient in their receptors
Prostanoids in immunity: Roles revealed by mice deficient in their receptors
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DOI：
10.1016/j.lfs.2003.09.025
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发表时间：
2003-12-05
期刊：
影响因子：
6.1
通讯作者：
Narumiya, S
中科院分区：
文献类型：
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作者：
Narumiya, S
前列腺素类药物包括前列腺素 (PG) 和血栓素 (TX)，是一组响应各种（通常是有害的）刺激而形成和释放的脂质介质。虽然前列腺素类药物在急性炎症反应中的作用是众所周知的，并且已经被广泛研究，但人们普遍认为它们在免疫方面的作用很小。部分原因是抑制前列腺素合成的非甾体类抗炎药对体内免疫过程几乎没有影响。前列腺素通过作用于 G 蛋白偶联受体家族来发挥作用。它们包括PGD受体、PGE受体的EP1、EP2、EP3和EN亚型、PGF受体、PGI受体和TX受体。我们分别培育了缺乏这些前列腺素受体的小鼠，并检查了它们在各种病理条件下的作用。这些研究表明，前列腺素类药物在免疫反应的不同部位或水平上起作用，并发挥许多（通常是相反的）作用。例如，使用EP4缺陷小鼠，我们发现刺激树突状细胞中的PGE(2)-EP4信号传导可促进其迁移和成熟，而刺激T细胞中的相同途径可有效抑制其活化和增殖。在患有右旋糖酐硫酸钠诱导的结肠炎（一种炎症性肠病模型）的小鼠肠道中，PGE(2) 介导的 T 细胞增殖抑制作用是明显的。在这里，我总结了我们通过这些研究和其他研究获得的发现。这些发现表明对前列腺素的选择性操纵。受体可能有助于治疗某些免疫性疾病。 (C) 2003 Elsevier Inc. 保留所有权利。
Prostanoids including prostaglandins (PGs) and thromboxanes (TX) are a group of lipid mediators formed and released in response to various, often noxious, stimuli. While the roles of prostanoids in acute inflammatory responses are well known and have been extensively studied, it is generally believed that they play very little in immunity. This is partly because non-steroidal anti-inflammatory drugs that inhibit prostanoid synthesis have little effects on immune processes in vivo. Prostanoids exert their actions by acting on a family of G-protein-coupled receptors. They include PGD receptor, EP1, EP2, EP3 and EN subtypes of PGE receptor, PGF receptor, PGI receptor and TX receptor. We generated mice deficient in each of these prostanoid receptors individually, and examined their roles under various pathological conditions. These studies have revealed that prostanoids works at various sites or levels of immune responses and exert many, often opposing, actions. For example, using EP4-deficient mice, we found that stimulation of the PGE(2)-EP4 signaling in dendritic cells facilitates their migration and maturation, while the stimulation of the same pathway in T cells potently suppresses their activation and proliferation. The latter action is evident in PGE(2)-mediated suppression of T cell proliferation in the gut of mice subjected to dextran sodium sulfate-induced colitis, a model of inflammatory bowel disease. Here I summarize our findings obtained by these and other studies. These findings suggest that selective manipulation of the prostanoid. receptors may be beneficial in treatment of certain immunological disorders. (C) 2003 Elsevier Inc. All rights reserved.