title: Role of prostaglandin D2 receptor CRTH2 in sustained eosinophil accumulation in the airways of mice with chronic asthma.
abstract: The prostaglandin D(2) (PGD(2))/CRTH2 pathway is important for eosinophil trafficking in vitro; however, genetic deficiency of CRTH2 does not suppress in vivo eosinophilic airway inflammation in acute models of asthma, and the role of CRTH2 in the pathogenesis of asthma is still ambiguous. Therefore, in the present study we explored whether the PGD(2)/CRTH2 pathway could affect the phenotypes of chronic asthma. Either CRTH2-deficient (CRTH2-/-) or wild-type mice were sensitized and exposed to ovalbumin (OVA) for 3 days (acute model) or 6 weeks (chronic model). While the magnitude of the acute eosinophilic inflammation was equivalent between CRTH2-/- and wild-type mice, the number of inflammatory cells and eosinophils in bronchoalveolar lavage fluid after chronic OVA exposure was significantly reduced in CRTH2-/- mice (18.0 ± 2.6 × 10(4) cells and 2.0 ± 0.5 × 10(4) cells) compared to wild-type mice (27.9 ± 2.5 × 10(4) cells and 6.8 ± 1.1 × 10(4) cells, p < 0.001). On the contrary, no difference was observed between CRTH2-/- and wild-type mice in terms of airway hyperresponsiveness or remodeling (goblet cell hyperplasia) in the chronic model of asthma. In conclusion, CRTH2 that mediates PGD(2) activity is essential for sustained eosinophilic inflammation in the airways, and its antagonists could exert an anti-inflammatory effect in chronic asthma.
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kagawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oguma
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shiomi
authors.forename: Koichi
authors.initials: K
authors.lastname: Sayama
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirai
authors.forename: Kinya
authors.initials: K
authors.lastname: Nagata
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.forename: Koichiro
authors.initials: K
authors.lastname: Asano
mesh_terms: D000818:Animals; D001249:Asthma / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004804:Eosinophils / Q000473:pathology; D020397:Goblet Cells / Q000378:metabolism / Q000473:pathology; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D014611:Vaccination
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D009077:Mucins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D016210:Methacholine Chloride; D010047:Ovalbumin; C036293:prostaglandin D2 receptor