D prostanoid receptor 2 (chemoattractant receptor–homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects on bronchial epithelial cells

• Published in: Journal of allergy and clinical immunology Vol. 135; no. 2; pp. 395 - 406.e7
• Main Authors: Stinson, Sally E., Amrani, Yassine, Brightling, Christopher E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2015; Elsevier Limited; Mosby
• Subjects: Adult; Airway Remodeling - genetics; Allergy and Immunology; Asthma; Asthma - diagnosis; Asthma - genetics; Asthma - immunology; Asthma - metabolism; Asthma and Lower Airway Disease; Biopsy; Bronchi - immunology; Bronchi - metabolism; Bronchi - pathology; Calcium - metabolism; Case-Control Studies; Cell Differentiation - genetics; Cell Movement; Cells, Cultured; Chronic obstructive pulmonary disease; Disease; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epithelial Cells - cytology; Epithelial Cells - metabolism; Expression; Female; Humans; Immunohistochemistry; Male; Middle Aged; Pathogenesis; prostaglandin D2; Protein expression; Proteins; Respiratory Function Tests; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; Risk Factors; Severity of Illness Index; Studies; Transcription Factors - genetics; Transcription Factors - metabolism; United Kingdom > UK; PGD2; DP1; Expression; prostaglandin D2; DP2; biopsy; CRTH2; DK-PGD2; asthma; immunohistochemistry; ALI; COPD; D prostanoid receptor 2; D prostanoid receptor 1; Air-liquid interface; DK-PGD 2; Chemoattractant receptor–homologous molecule expressed on T H2 cells; 13, 14-Dihydro-15-keto prostaglandin D 2; PGD 2; Chronic obstructive pulmonary disease; prostaglandin D 2; prostaglandin D
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2014.08.027

The D prostanoid receptor 2 (DP2; also known as chemoattractant receptor–homologous molecule expressed on TH2 cells) is implicated in the pathogenesis of asthma, but its expression within bronchial biopsy specimens is unknown. We sought to investigate the bronchial submucosal DP2 expression in asthmatic patients and healthy control subjects and to explore its functional role in epithelial cells. DP2 protein expression was assessed in bronchial biopsy specimens from asthmatic patients (n = 22) and healthy control subjects (n = 10) by using immunohistochemistry and in primary epithelial cells by using flow cytometry, immunofluorescence, and quantitative RT-PCR. The effects of the selective DP2 agonist 13, 14-dihydro-15-keto prostaglandin D2 on epithelial cell migration and differentiation were determined. Numbers of submucosal DP2+ cells were increased in asthmatic patients compared with those in healthy control subjects (mean [SEM]: 78 [5] vs 22 [3]/mm2 submucosa, P < .001). The bronchial epithelium expressed DP2, but its expression was decreased in asthmatic patients compared with that seen in healthy control subjects (mean [SEM]: 21 [3] vs 72 [11]/10 mm2 epithelial area, P = .001), with similar differences observed in vitro by primary epithelial cells. Squamous metaplasia of the bronchial epithelium was increased in asthmatic patients and related to decreased DP2 expression (rs = 0.69, P < .001). 13, 14-Dihydro-15-keto prostaglandin D2 promoted epithelial cell migration and at air-liquid interface cultures increased the number of MUC5AC+ and involucrin-positive cells, which were blocked with the DP2-selective antagonist AZD6430. DP2 is expressed by the bronchial epithelium, and its activation drives epithelial differentiation, suggesting that in addition to its well-characterized role in inflammatory cell migration, DP2 might contribute to airway remodeling in asthmatic patients.