Year: 2015
Type: dissertation
Abstract: CRTh2 (DP2) is implicated in the pathogenesis of asthma; however, currently there\nis a lack of data describing the protein expression of CRTh2 in bronchial biopsies in\nasthma. This has limited the cell types that CRTh2 function has been explored\nwithin. A thorough understanding of CRTh2 expression within the airways and\nwhether changes in receptor expression correlates with disease severity, may aid in\nthe design of future CRTh2 antagonist clinical studies.\nThis study aimed to investigate the expression of CRTh2 expression in bronchial\nbiopsies of subjects with asthma and healthy controls. The novel finding that\nCRTh2 was expressed on bronchial epithelial cells in asthma prompted further\ninvestigation into the expression and activation of CRTh2 on bronchial epithelial\ncells in vitro, using the selective CRTh2 agonist 13, 14-dihydro-15-keto\nprostaglandin D2 (DK-PGD2) and the CRTh2 selective antagonist AZD6430.\nThis study is the first to describe differential CRTh2 expression within bronchial\ntissue in asthma compared to healthy controls. The number of sub-mucosal\nCRTh2+ cells was found to be increased in asthma compared to healthy controls.\nCRTh2 was found to be expressed on the bronchial epithelium and its expression\nwas decreased in asthma compared to healthy controls with similar differences\nobserved in vitro by primary epithelial cells. Squamous metaplasia of the bronchial\nepithelium was increased in asthma and related to decreased CRTh2 expression.\nDK-PGD2 promoted epithelial cell migration, and in air-liquid interface cultures\nincreased the number of MUC5AC+ and involucrin+ cells, which were blocked with\nthe CRTh2 antagonist, AZD6430.\nThis study describes the novel findings that CRTh2 is expressed by the bronchial\nepithelium in both health and asthma, and its activation drives epithelial\ndifferentiation. These data suggests that CRTh2 could contribute to airway\nremodelling in asthma and this information may contribute to the understanding of\nthe effects of CRTh2 antagonists in asthmatic patients.
Source: Figshare
Author: Sally Stinson
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: AstraZeneca, University of Leicester
OpenAlex ID: W829816953