Tanaka H, Nagai H
Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu City, Gifu 502-8585, Japan.
Nihon Yakurigaku Zasshi. 2001 Apr;117(4):262-6.
Allergic inflammation is orchestrated by mainly antigen-specific CD4+ T cells, eosinophils and mast cells, which is a characteristic feature of bronchial asthma, rhinitis and atopic dermatitis. Prostanoids are one of the arachidonic metabolites, which are produced by a variety of inflammatory cells upon stimulation and are thought to be involved in the pathogenesis of diseases as well as the regulation of homeostasis. We investigated the role of a prostanoid, prostaglandin D2 (PGD2), in the pathogenesis of allergic bronchial asthma using its receptor, DP, gene-deficient mice. We found that the disruption of the DP gene attenuated the allergen-induced airway eosinophilic inflammation, Th2 type cytokine production and bronchial hyperresponsiveness to cholinergic stimuli, suggesting that PGD2 is an important mediator of allergic asthma. In contrast, the treatment of non-steroidal anti-inflammatory agents, which are known to be inhibitors of cyclooxygenases, did not inhibit or instead exaggerated these responses in asthmatics or experimental animal models, indicating that there are regulatory prostanoids in allergic inflammation. Recently, strategies of gene manipulation such as the "knockout" or "transgenic" techniques are important means to understand the role of a certain functional molecule. These approaches and the development of their antagonists/inhibitors could help us to understand the function of prostanoids in the pathophysiology of allergic disorders.
过敏性炎症主要由抗原特异性CD4 + T细胞、嗜酸性粒细胞和肥大细胞协调,这是支气管哮喘、鼻炎和特应性皮炎的特征。前列腺素是花生四烯酸代谢产物之一,由多种炎症细胞在刺激后产生,被认为参与疾病的发病机制以及体内稳态的调节。我们使用前列腺素D2(PGD2)受体DP基因缺陷小鼠研究了前列腺素PGD2在过敏性支气管哮喘发病机制中的作用。我们发现DP基因的破坏减弱了变应原诱导的气道嗜酸性粒细胞炎症、Th2型细胞因子产生以及支气管对胆碱能刺激的高反应性,这表明PGD2是过敏性哮喘的重要介质。相反,已知作为环氧化酶抑制剂的非甾体抗炎药治疗并未抑制哮喘患者或实验动物模型中的这些反应,反而使其加剧,这表明在过敏性炎症中存在调节性前列腺素。最近,诸如“基因敲除”或“转基因”技术等基因操作策略是了解特定功能分子作用的重要手段。这些方法及其拮抗剂/抑制剂的开发可以帮助我们了解前列腺素在过敏性疾病病理生理学中的功能。