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

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.

• 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)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• TFDP2 protein, human
• Transcription Factors
• Calcium

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)