D prostanoid receptor 2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects on bronchial epithelial cells.
journal contributionposted on 10.07.2015, 10:55 by Sally E. Stinson, Yassine Amrani, Christopher E. Brightling
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: Numbers of submucosal DP2(+) cells were increased in asthmatic patients compared with those in healthy control subjects (mean [SEM]: 78  vs 22 /mm(2) 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  vs 72 /10 mm(2) 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. CONCLUSIONS: 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.
CitationJournal of Allergy and Clinical Immunology, 2015, 135 (2), pp. 395-406
Author affiliation/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation
VersionVoR (Version of Record)
Published inJournal of Allergy and Clinical Immunology
PublisherElsevier for American Academy of Allergy, Asthma and Immunology
Expressionasthmabiopsyimmunohistochemistryprostaglandin D(2)AdultAirway RemodelingAsthmaBiopsyBronchiCalciumCase-Control StudiesCell DifferentiationCell MovementCells, CulturedDNA-Binding ProteinsEpithelial CellsFemaleHumansImmunohistochemistryMaleMiddle AgedRespiratory Function TestsRespiratory MucosaRisk FactorsSeverity of Illness IndexTranscription Factors