Caveolin-1 Controls Airway Epithelial Barrier Function. Implications for Asthma

• Published in: American journal of respiratory cell and molecular biology Vol. 49; no. 4; pp. 662 - 671
• Main Authors: Hackett, Tillie-Louise, de Bruin, Harold G., Shaheen, Furquan, van den Berge, Maarten, van Oosterhout, Antoon J., Postma, Dirkje S., Heijink, Irene H.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.10.2013
• Subjects: Adherens Junctions - genetics; Adherens Junctions - immunology; Adherens Junctions - metabolism; Adolescent; Adult; Animals; Asthma - genetics; Asthma - immunology; Asthma - metabolism; beta Catenin - genetics; beta Catenin - immunology; beta Catenin - metabolism; Bronchi - immunology; Bronchi - metabolism; Cadherins - genetics; Cadherins - immunology; Cadherins - metabolism; Caveolin 1 - genetics; Caveolin 1 - immunology; Caveolin 1 - metabolism; Cell Adhesion - genetics; Cell Adhesion - immunology; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Child; Down-Regulation; Epidermal Growth Factor - genetics; Epidermal Growth Factor - immunology; Epidermal Growth Factor - metabolism; Epithelial Cells - immunology; Epithelial Cells - metabolism; Female; Humans; Male; Pyroglyphidae - immunology; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; Up-Regulation
• ISSN: 1044-1549; 1535-4989; 1535-4989
• DOI: 10.1165/rcmb.2013-0124OC

The molecular basis for airway epithelial fragility in asthma has remained unclear. We investigated whether the loss of caveolin-1, the major component of caveolae and a known stabilizer of adherens junctions, contributes to epithelial barrier dysfunction in asthma. We studied the expression of caveolin-1 and adhesion molecules E-cadherin and β-catenin in airway sections, and we cultured bronchial epithelial cells from patients with asthma and from healthy control subjects. To determine the functional role of caveolin-1, we investigated the effects of caveolin-1 up-regulation and down-regulation on E-cadherin expression, barrier function, and proallergic activity in the human bronchial epithelial cell lines 16HBE and BEAS-2B. The membrane expression of caveolin-1 was significantly lower in airway epithelia from patients with asthma than from subjects without asthma, and this lower expression was maintained in vitro upon air-liquid interface and submerged culturing. Importantly, reduced caveolin-1 expression was accompanied by a loss of junctional E-cadherin and β-catenin expression, disrupted epithelial barrier function, and increased levels of the proallergic cytokine thymic stromal lymphopoietin (TSLP). Furthermore, E-cadherin redistribution upon exposure to epidermal growth factor or house dust mite was paralleled by the internalization of caveolin-1 in 16HBE cells. These effects appear to be causally related, because the short, interfering RNA down-regulation of caveolin-1 resulted in the delocalization of E-cadherin and barrier dysfunction in 16HBE cells. Moreover, caveolin-1 overexpression improved barrier function and reduced TSLP expression in BEAS-2B cells. Together, our data demonstrate a crucial role for caveolin-1 in epithelial cell-cell adhesion, with important consequences for epithelial barrier function and the promotion of Th2 responses in asthma.