Corticosteroid and long-acting ß-agonist therapy reduces epithelial goblet cell metaplasia.
| Autor: | Lachowicz-Scroggins ME; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA., Finkbeiner WE; Department of Pathology, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA., Gordon ED; Department of Medicine Division of Pulmonary/Critical Care Medicine University of California San Francisco, San Francisco, CA, USA., Yuan S; The David Rockefeller Graduate Program, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY, USA., Zlock L; Department of Pathology, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA., Bhakta NR; Department of Medicine Division of Pulmonary/Critical Care Medicine University of California San Francisco, San Francisco, CA, USA., Woodruff PG; Department of Medicine Division of Pulmonary/Critical Care Medicine University of California San Francisco, San Francisco, CA, USA., Fahy JV; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.; Department of Medicine Division of Pulmonary/Critical Care Medicine University of California San Francisco, San Francisco, CA, USA., Boushey HA; Department of Medicine Division of Pulmonary/Critical Care Medicine University of California San Francisco, San Francisco, CA, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2017 Dec; Vol. 47 (12), pp. 1534-1545. Date of Electronic Publication: 2017 Sep 26. |
| DOI: | 10.1111/cea.13015 |
| Abstrakt: | 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 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/FOXa2, gene expression and protein production of MUC5AC/MUC5B 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 FOXa2 gene expression and up-regulation of SPDEF, alterations in gene and protein measures of MUC5AC and MUC5B and induction of GCM. The addition of SM synergistically modified the effects of FP modestly-only for gel-forming mucin MUC5AC. In bronchial epithelial cells recovered from asthmatic vs healthy human subjects, we found FOXa2 and MUC5B gene expression to be reduced and SPDEF and MUC5AC 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 FOXa2 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 (© 2017 John Wiley & Sons Ltd.) |
| Databáze: | MEDLINE |
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