title: Role of Prostaglandin D2 and DP1 Receptor on Japanese Cedar Pollen-Induced Allergic Rhinitis in Mice.
abstract: Although we previously demonstrated the contribution of the DP1receptor in nasal obstruction using animals sensitized with ovalbumin in the presence of adjuvant, the contribution of the DP1receptor in sneezing is unclear. Here, we developed a mouse model of Japanese cedar (JC:Cryptomeria japonica) pollinosis to evaluate the symptoms of sneezing. To achieve this, we used JC pollen crude extract in the absence of adjuvant to sensitize mice to develop a model closer to the pathophysiology of human JC pollinosis. The immunologic and pharmacologic features of this model are highly similar to those observed in JC pollinosis in humans. Using this model, we found that DP1receptor antagonists suppressed JC pollen extract-induced sneezing and that a DP1receptor agonist induced sneezing. Moreover, JC pollen extract-induced sneezing was diminished in DP1receptor knockout mice. In conclusion, we developed a novel mouse model of allergic rhinitis that closely mimics human JC pollinosis. A strong contribution of DP1receptor signaling to sneezing was demonstrated using this model, suggesting that DP1receptor antagonists could suppress sneezing and nasal obstruction, and therefore these agents could be a new therapeutic option for allergic rhinitis.
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu (Y.N., N.I., H.T.), Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka (Y.N., Y.K., K.G., S.F., Y.T., M.S.), and Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu (N.I., H.T.), Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu (Y.N., N.I., H.T.), Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka (Y.N., Y.K., K.G., S.F., Y.T., M.S.), and Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu (N.I., H.T.), Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Kidani
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu (Y.N., N.I., H.T.), Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka (Y.N., Y.K., K.G., S.F., Y.T., M.S.), and Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu (N.I., H.T.), Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Goto
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu (Y.N., N.I., H.T.), Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka (Y.N., Y.K., K.G., S.F., Y.T., M.S.), and Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu (N.I., H.T.), Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Furue
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu (Y.N., N.I., H.T.), Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka (Y.N., Y.K., K.G., S.F., Y.T., M.S.), and Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu (N.I., H.T.), Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu (Y.N., N.I., H.T.), Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka (Y.N., Y.K., K.G., S.F., Y.T., M.S.), and Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu (N.I., H.T.), Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu (Y.N., N.I., H.T.), Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka (Y.N., Y.K., K.G., S.F., Y.T., M.S.), and Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu (N.I., H.T.), Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu (Y.N., N.I., H.T.), Discovery Research Laboratory for Innovative Frontier Medicines, Shionogi & Co., Ltd., Toyonaka (Y.N., Y.K., K.G., S.F., Y.T., M.S.), and Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu (N.I., H.T.), Japan michitaka.shichijou@shionogi.co.jp hirotnk@gifu-pu.ac.jp.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Shichijo
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D032485:Cryptomeria / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015508:Nasal Obstruction / Q000209:etiology / Q000517:prevention & control; D010936:Plant Extracts; D011058:Pollen / Q000276:immunology*; D011448:Prostaglandin Antagonists / Q000627:therapeutic use*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000235:genetics; D065631:Rhinitis, Allergic / Q000503:physiopathology*; D012912:Sneezing
chemical_list: D018926:Anti-Allergic Agents; D016207:Cytokines; D010936:Plant Extracts; D011448:Prostaglandin Antagonists; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C527097:prostanoid D receptor 1, mouse; D007073:Immunoglobulin E; C036293:prostaglandin D2 receptor