Abstract | 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 [5] vs 22 [3]/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 [3] vs 72 [11]/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.
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Authors | Sally E Stinson, Yassine Amrani, Christopher E Brightling |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 135
Issue 2
Pg. 395-406
(Feb 2015)
ISSN: 1097-6825 [Electronic] United States |
PMID | 25312757
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- DNA-Binding Proteins
- TFDP2 protein, human
- Transcription Factors
- Calcium
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Topics |
- Adult
- Airway Remodeling
(genetics)
- Asthma
(diagnosis, genetics, immunology, metabolism)
- Biopsy
- Bronchi
(immunology, metabolism, pathology)
- Calcium
(metabolism)
- Case-Control Studies
- Cell Differentiation
(genetics)
- Cell Movement
- Cells, Cultured
- DNA-Binding Proteins
(genetics, metabolism)
- Epithelial Cells
(cytology, metabolism)
- Female
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Respiratory Function Tests
- Respiratory Mucosa
(immunology, metabolism, pathology)
- Risk Factors
- Severity of Illness Index
- Transcription Factors
(genetics, metabolism)
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