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Corticosteroid and long‐acting ß‐agonist therapy reduces epithelial goblet cell metaplasia
Author(s) -
LachowiczScroggins M. E.,
Finkbeiner W. E.,
Gordon E. D.,
Yuan S.,
Zlock L.,
Bhakta N. R.,
Woodruff P. G.,
Fahy J. V.,
Boushey H. A.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13015
Subject(s) - goblet cell , metaplasia , foxa2 , gene expression , epithelium , agonist , endocrinology , medicine , fluticasone propionate , corticosteroid , immunology , biology , receptor , pathology , gene , biochemistry
Summary Background Bronchial epithelial goblet cell metaplasia ( GCM ) with hyperplasia is a prominent feature of asthma, but the effects of treatment with corticosteroids alone or in combination with a long‐acting β 2 ‐adrenergic receptor agonist ( LABA ) on GCM in the bronchial epithelium are unknown. Objectives To determine whether corticosteroid alone or in combination with a LABA alters protein and gene expression pathways associated with IL ‐13–induced goblet cell metaplasia. Results We evaluated the effects of fluticasone propionate ( FP ) and of salmeterol ( SM ), on the response of well‐differentiated cultured bronchial epithelial cells to interleukin‐13 ( IL ‐13). Outcome measures included gene expression of SPDEF / FOX a2 , gene expression and protein production of MUC 5 AC / MUC 5B and morphologic appearance of cultured epithelial cell sheets. We additionally analysed expression of these genes in bronchial epithelial brushings from healthy, steroid‐naïve asthmatic and steroid‐treated asthmatic subjects. In cultured airway epithelial cells, FP treatment inhibited IL ‐13–induced suppression of FOX a2 gene expression and up‐regulation of SPDEF , alterations in gene and protein measures of MUC 5 AC and MUC 5B and induction of GCM . The addition of SM synergistically modified the effects of FP modestly—only for gel‐forming mucin MUC 5 AC . In bronchial epithelial cells recovered from asthmatic vs healthy human subjects, we found FOX a2 and MUC 5B gene expression to be reduced and SPDEF and MUC 5 AC gene expression to be increased; these alterations were not observed in bronchial epithelial cells recovered after treatment with inhaled corticosteroids. Conclusion and Clinical Relevance Corticosteroid treatment inhibits IL ‐13–induced GCM of the airways in asthma, possibly through its effects on SPDEF and FOX a2 regulation of mucin gene expression. These effects are modestly augmented by the addition of a long‐acting ß‐agonist. As we found evidence for drug treatment counteracting the effects of IL ‐13 on the epithelium, we conclude that further exploration into the mechanisms by which corticosteroids and long‐acting β 2 ‐adrenergic agonists confer protection against pathologic airway changes is warranted.