IL‐13‐inducedMUC5ACproduction and goblet cell differentiation is steroid resistant in human airway cells
- 20 September 2011
- journal article
- research article
- Published by Wiley in Clinical and Experimental Allergy
- Vol. 41 (12), 1747-1756
- https://doi.org/10.1111/j.1365-2222.2011.03852.x
Abstract
Background Glucocorticosteroids (GCS) are used to treat bronchial asthma, but are not uniformly effective, especially in severe asthma. IL-13 is a T helper type 2 cytokine implicated in the pathogenesis of asthma, and IL-13 induces mucus production and goblet cell hyperplasia in airway epithelial cells. The effect of GCS on IL-13-induced mucin production is not well characterized. Objective The aim of this study was to evaluate the effect of dexamethasone (Dex), a potent synthetic GCS, on IL-13-induced MUC5AC mucin expression and goblet cell proliferation in differentiated normal human bronchial epithelial cells (NHBECs). Methods NHBECs were cultured for 14 days at an air–liquid interface with IL-13, with or without Dex. MUC5AC protein secretion and mRNA expression was determined using ELISA and quantitative real-time PCR. IL-8 production was assayed using ELISA. Histochemical analysis was performed using H&E and periodic acid-Schiff stain, and MUC5AC immunostaining. Results Although Dex dose dependently inhibited IL-8 release induced by 5 ng/mL IL-13, Dex 0.001–1 μg/mL had no effect on IL-13 induced MUC5AC protein secretion or mRNA expression. Dex paradoxically increased MUC5AC induced by IL-13 at 0.5 and 1 ng/mL, but had no effect alone or with IL-13 at 0.1 ng/mL. Dex 0.001–1 μg/mL did not inhibit the differentiation of cells into goblet cells and MUC5AC-positive cells induced by IL-13. Conclusion and Clinical Relevance Dex at therapeutic concentrations did not inhibit the effects of IL-13 on goblet cell differentiation, characteristic of severe asthma. Paradoxically, MUC5AC production was increased with lower dose IL-13 exposure. This may lead to airway mucus obstruction commonly seen in life-threatening asthma.Keywords
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