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Am. J. Respir. Cell Mol. Biol., Volume 26, Number 3, March, 2002 341-347

Modulation of Cadherin and Catenins Expression by Tumor Necrosis Factor-alpha and Dexamethasone in Human Bronchial Epithelial Cells

Nathalie Carayol, Alison Campbell, Isabelle Vachier, Brigitte Mainprice, Jean Bousquet, Philippe Godard, and Pascal Chanez

Clinique des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Montpellier, France

Asthma is an inflammatory disease, and the epithelial mesenchymal unit appears to be of importance in regulating the disease mechanisms. Cell-cell adhesion plays an important role in tissue morphogenesis and homeostasis and is commonly mediated by cadherins, a family of Ca2+-dependent transmembrane adhesion receptors. The cadherin family is involved in control of the cellular architecture. Proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha are involved in asthma and may interfere with epithelial integrity. In the present study, we investigated the role of TNF-alpha and dexamethasone on the expression of E-cadherin, beta -catenin, and gamma -catenin. We used two bronchial epithelial cell models: primary small airway epithelial cell cultures and primary culture obtained from human bronchial tubes. After 48 h of TNF-alpha stimulation with or without dexamethasone expression of E-cadherin, beta -catenin and gamma -catenin were analyzed using Western blot analysis and immunofluorescence. This study showed a decrease in the expression of adhesion molecules in both epithelial cell cultures after stimulation. Dexamethasone and anti-TNF-alpha inhibited this effect. In unstimulated cells, E-cadherin and beta - and gamma -catenin expression was membranous, expressed only on the lateral cell wall with minimal cytoplasmic expression. Immunoreactivity was cytoplasmic in stimulated cells. We demonstrated, using Western blot analysis and immunofluorescence, that proinflammatory cytokines could be responsible for structural damage to the epithelium and that this process was potentially reversed by steroids.

Abbreviations: bovine serum albumin, BSA; ethylenediaminetetraacetic acid, EDTA; human bronchial epithelial cells, HBEC; human umbilical vein cells, HUVEC; interferon, IFN; interleukin, IL; nuclear factor, NF; phosphate-buffered saline, PBS; small airway epithelial cell, SAEC; tumor necrosis factor, TNF.




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