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

Am J Respir Cell Mol Biol. 2013 Oct;49(4):662-71. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / genetics
  • Adherens Junctions / immunology
  • Adherens Junctions / metabolism
  • Adolescent
  • Adult
  • Animals
  • Asthma / genetics
  • Asthma / immunology
  • Asthma / 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
  • beta Catenin / genetics
  • beta Catenin / immunology
  • beta Catenin / metabolism


  • Cadherins
  • Caveolin 1
  • Cell Adhesion Molecules
  • beta Catenin
  • Epidermal Growth Factor