[Inflammation-allergy and prostanoids. (2). The role of prostanoids in allergic inflammation].
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.
Tanaka
H
H
Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu City, Gifu 502-8585, Japan. hirotnk@gifu-pu.ac.jp
Nagai
H
H
D000818:Animals; D001249:Asthma / Q000209:etiology; D016535:Bronchial Hyperreactivity / Q000209:etiology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D006969:Hypersensitivity, Immediate / Q000209:etiology; D007249:Inflammation / Q000209:etiology*; D008407:Mast Cells / Q000502:physiology; D015230:Prostaglandin D2 / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*
D016207:Cytokines; D011453:Prostaglandins; D015230:Prostaglandin D2