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Am J Physiol Lung Cell Mol Physiol 291: L1220-L1231, 2006. First published July 28, 2006; doi:10.1152/ajplung.00511.2005
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Dexamethasone inhibits the action of TNF on ENaC expression and activity

André Dagenais,1,2 Rosalie Fréchette,1 Marie-Eve Clermont,1 Chantal Massé,1 Anik Privé,1 Emmanuelle Brochiero,1,2 and Yves Berthiaume1,2

1Centre de recherche, Centre hospitalier de l'Université de Montréal (CHUM)-Hôtel-Dieu, and 2Département de médecine, Université de Montréal, Montréal, Québec, Canada

Submitted 5 December 2005 ; accepted in final form 21 July 2006

We have reported that TNF, a proinflammatory cytokine present in several lung pathologies, decreases the expression and activity of the epithelial Na+ channel (ENaC) by ~70% in alveolar epithelial cells. Because dexamethasone has been shown to upregulate ENaC mRNA expression and is well known to downregulate proinflammatory genes, we tested if it could alleviate the effect of TNF on ENaC expression and activity. In cotreatment with TNF, we found that dexamethasone reversed the inhibitory effect of TNF and upregulated {alpha}, beta, and {gamma}ENaC mRNA expression. When the cells were pretreated for 24 h with TNF before cotreatment, dexamethasone was still able to increase {alpha}ENaC mRNA expression to 1.8-fold above control values. However, in these conditions, beta and {gamma}ENaC mRNA expression was reduced to 47% and 14%, respectively. The potential role of TNF and dexamethasone on {alpha}ENaC promoter activity was tested in A549 alveolar epithelial cells. TNF decreased luciferase (Luc) expression by ~25% in these cells, indicating that the strong diminution of {alpha}ENaC mRNA must be related to posttranscriptional events. Dexamethasone raised Luc expression by fivefold in the cells and augmented promoter activity by 2.77-fold in cotreatment with TNF. In addition to its effect on {alpha}ENaC gene expression, dexamethasone was able to maintain amiloride-sensitive current as well as the liquid clearance abilities of TNF-treated cells within the normal range. All these results suggest that dexamethasone alleviates the downregulation of ENaC expression and activity in TNF-treated alveolar epithelial cells.

Na+ channel; lung; transepithelial current; inflammation; steroid


Address for reprint requests and other correspondence: A. Dagenais, Centre de recherche, CHUM-Hôtel-Dieu, 3850 St-Urbain, Montreal, Quebec, Canada H2W 1T7 (e-mail: andre.dagenais.chum{at}ssss.gouv.qc.ca)




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Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium
Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1739 - C1745.
[Abstract] [Full Text] [PDF]


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