Referenced in: none

Automatically associated channels: Kir6.2

Title: Downregulation of ENaC activity and expression by TNF-alpha in alveolar epithelial cells.

Authors: André Dagenais, Rosalie Fréchette, Yuko Yamagata, Toshiyuki Yamagata, Jean-François Carmel, Marie-Eve Clermont, Emmanuelle Brochiero, Chantal Massé, Yves Berthiaume

Journal, date & volume: Am. J. Physiol. Lung Cell Mol. Physiol., 2004 Feb , 286, L301-11

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14514522

Abstract
Sodium absorption by an amiloride-sensitive channel is the main driving force of lung liquid clearance at birth and lung edema clearance in adulthood. In this study, we tested whether tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine involved in several lung pathologies, could modulate sodium absorption in cultured alveolar epithelial cells. We found that TNF-alpha decreased the expression of the alpha-, beta-, and gamma-subunits of epithelial sodium channel (ENaC) mRNA to 36, 43, and 16% of the controls after 24-h treatment and reduced to 50% the amount of alpha-ENaC protein in these cells. There was no impact, however, on alpha(1) and beta(1) Na(+)-K(+)-ATPase mRNA expression. Amiloride-sensitive current and ouabain-sensitive Rb(+) uptake were reduced, respectively, to 28 and 39% of the controls. A strong correlation was found at different TNF-alpha concentrations between the decrease of amiloride-sensitive current and alpha-ENaC mRNA expression. All these data show that TNF-alpha, a proinflammatory cytokine present during lung infection, has a profound influence on the capacity of alveolar epithelial cells to transport sodium.