The potential of selected prostanoid receptors as targets in a new therapeutic strategy for allergy and immune diseases.
Allergy and immune diseases including asthma, atopic dermatitis, rhinitis, and autoimmune diseases have been treated mainly with steroid based therapy that has multiple side effects. Even then, these allergic diseases are sometimes still not easy to control. Therefore, new effective treatments with fewer side effects are expected to be developed. Prostanoids consisting of prostaglandins and thromboxane are cyclooxygenase metabolites of arachidonic acid. They exert a range of actions mediated through their respective receptors expressed in target cells. In the skin, a wide variety of prostanoids and their receptors are highly expressed under pathophysiological conditions. However, their roles have not been well clarified. Recent developments in molecular biology have enabled us to investigate the physiological roles for each receptor via the disruption of the respective gene in combination with receptor selective compounds. It has been demonstrated that each prostanoid receptor has multiple functions whose expression is regulated in a context dependent manner, sometimes resulting in opposite, excitatory and inhibitory, outcomes. The balance of prostanoid production and receptor expression is important for homeostasis of the human body. Here, we review new findings on the roles of prostanoids in allergy and immune diseases, focusing on skin disorders as a representative, and discuss the clinical potentials of receptor-selective drugs.
Kabashima
Kenji
K
Department of Dermatology, University of Environmental and Occupational Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. kkabashi@med.uoeh-u.ac.jp
Tokura
Yoshiki
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000503:physiopathology; D007154:Immune System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D011453:Prostaglandins / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011982:Receptors, Prostaglandin