Caveolin-1 controls airway epithelial barrier function. Implications for asthma.

TitleCaveolin-1 controls airway epithelial barrier function. Implications for asthma.
Publication TypeJournal Article
Year of Publication2013
AuthorsHackett, T-L, de Bruin, HG, Shaheen, F, van den Berge, M, van Oosterhout, AJ, Postma, DS, Heijink, IH
JournalAm J Respir Cell Mol Biol
Date Published2013 Oct
KeywordsAdherens Junctions, Adolescent, Adult, Animals, Asthma, beta Catenin, Bronchi, Cadherins, Caveolin 1, Cell Adhesion, Cell Adhesion Molecules, Child, Down-Regulation, Epidermal Growth Factor, Epithelial Cells, Female, Humans, Male, Pyroglyphidae, Respiratory Mucosa, Th2 Cells, Up-Regulation

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.

Alternate JournalAm. J. Respir. Cell Mol. Biol.
PubMed ID23742006
Grant List / / Canadian Institutes of Health Research / Canada