The DP receptor, allergic inflammation and asthma.
Prostaglandin (PG) D(2) is the major cyclooxygenase metabolite of arachidonic acid produced by mast cells in response to allergen in diseases, such as asthma, atopic dermatitis, allergic rhinitis and allergic conjunctivitis. However, whether PGD(2) regulates allergic process per se, and, if so, whether it facilitates or down-regulates the disease process has remained unknown. PGD(2) exerts its actions by binding to two types of specific cell surface receptor. One is DP (the PGD receptor) and the other is chemoattractant receptor-homologous molecule expressed on Th2. Between the two, the DP receptor has been better characterized since its cDNA cloning in 1994, and novel class of DP antagonists have been and are being developed. Furthermore, mice deficient in DP were generated and have been subjected to several models of allergic diseases to reveal the role of PGD(2) in allergy. In this article, we summarize these findings and provide an overview of the current status of the DP receptor research to discuss the therapeutic potential of modulating the PGD(2)-DP pathway in allergic diseases.
Kabashima
Kenji
K
Faculty of Medicine, 2nd Department of Pharmacology, Kyoto University, Yoshida-Konoe cho, Sakyo-ku, Kyoto 606-8501, Japan.
Narumiya
Shuh
S
D000595:Amino Acid Sequence; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000517:prevention & control; D002460:Cell Line; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000517:prevention & control; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008024:Ligands; D008969:Molecular Sequence Data; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction
D008024:Ligands; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor