TY - JOUR T1 - Corticosteroids improve airway epithelial regeneration and restore oxidative stress-induced epithelial barrier dysfunction JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - 4737 AU - Irene Heijink AU - Maarten van den Berge AU - Nathalie Kliphuis AU - Nick ten Hacken AU - Dirkje Postma AU - Antoon van Oosterhout Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/4737.abstract N2 - Background: The airway epithelium plays an emerging role in the pathogenesis of respiratory diseases. Its barrier function may be defective in asthma and COPD. Aims: To study the protective effect of inhaled corticosteroid budesonide (BUD) on different aspects of epithelial integrity, including cell-cell contact formation, regeneration upon wounding and barrier function during mucociliary differentiation at the air-liquid interface (ALI). Methods: We studied the effect of BUD (10-7-10-9M) on epithelial resistance during ALI culture, upon exposure to H2O2 and/or cigarette smoke extract (CSE) and upon wounding by electroporation using the ECIS system in 16HBE cells and primary human bronchial epithelial cells (PBECs) from asthma patients, COPD patients and healthy controls. Results: BUD significantly improved the recovery of cell-cell contacts upon wounding in 16HBE cells. Oxidative stress induced a transient defect in 16HBE barrier function, which was attenuated by BUD and likely mediated by the protection against EGFR-dependent disruption of junctions. In PBECs, CSE exposure resulted in a substantial barrier dysfunction, with no significant differences between the subject groups. BUD significantly improved baseline resistance and counteracted the CSE-induced barrier dysfunction. Finally, BUD slightly but significantly increased epithelial barrier function during ALI-culture, but did not affect MUC5A/C production. Conclusions: BUD improves the restoration of epithelial cell-cell contacts upon oxidative stress and wounding and may thus provide beneficial effects on epithelial barrier function, repair and remodelling in the airways of asthma and COPD patients. ER -