Corticosteroid and Long-Acting ß-Agonist Therapy Reduces Epithelial Goblet Cell Metaplasia

Abstract

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 β₂-adrenergic receptor agonist (LABA) on GCM in the bronchial epithelium are unknown.

Objectives

To determine if corticosteroid alone or in combination with a LABA alter 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 analyzed 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 upregulation 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 SPEDF 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 counter-acting the effects of IL-13 on the epithelium, we conclude that further exploration into the mechanisms by which corticosteroids and long-acting β₂-adrenergic agonists confer protection against pathologic airway changes is warranted.

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2xmObsS