Epigallocatechin‐3‐Gallate inhibits the effects of TGF‐Beta and IL‐1B on ENaC expression in human alveolar epithelial cells.

Abstract

Acute Lung Injury (ALI) is major clinical problem in the United States, affecting over 200,000 Americans a year. Increased mortality in ALI is attributed to pulmonary edema and decreased net fluid transport. Previous clinical studies from ALI patients have correlated the decrease net fluid transport with decreased expression of epithelium sodium channels (ENaC). Therefore drugs that enhance ENaC expression offer considerable therapeutic promise in ALI. Epigallocatechin‐3‐Gallate (EGCG), a green tea extract, has been shown to have potent anti‐inflammatory effects. However, its effect on ENaC expression in response to proinflammatory cytokines in ALI has not been shown. In this study, we investigated the hypothesis that EGCG rescues human alveolar epithelial cell (A549) ENaC expression following proinflammatory cytokine (IL‐1β and TGFβ) treatment. To test this, A549 cells were treated with TGF‐β and IL‐1β in the presence or absence of EGCG. Cell lysates as well as supernatants were collected for protein analysis. EGCG treatments resulted in increased expression of the alpha and beta subunits of ENaC in response to both TGF‐ β and IL‐ β. Further, EGCG treatments resulted in decreased cytokine secretion mediated through decreased NF‐kappaB and p‐38 MAP kinase activity in comparison to control. Our data suggests that EGCG up regulates ENaC, a major sodium channel involved in resolution of pulmonary edema in ALI.