Referenced in: none

Automatically associated channels: ClC2 , ClC4

Title: Interferon-gamma regulates ClC-2 chloride channel in lung epithelial cells.

Authors: Shijian Chu, Carol J Blaisdell, Penelope Bamford, Thomas J Ferro

Journal, date & volume: Biochem. Biophys. Res. Commun., 2004 Nov 5 , 324, 31-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15464978

Abstract
Epithelial Cl(-) channels mediate Cl(-) and fluid secretion in the lung. In cystic fibrosis, aberrant Cl(-) secretion is one of the major causes for lung fluid imbalance. Regulation of Cl(-) channels is therefore an important issue in the lung. IFN-gamma regulates Na(+) and Cl(-) channels and fluid transport in the lung, but the mechanisms involved in these regulations are not clear. In expression studies, we found that IFN-gamma increased ClC-2 transcripts in Calu-3 cells. Studies of the promoter identified a minimal promoter which interacts with transcription factors Sp1 and Sp3. However, reporter gene assays showed that IFN-gamma did not activate the promoter. Instead, IFN-gamma significantly increased ClC-2 transcript stability. Using Ussing chamber experiments, we demonstrate that IFN-gamma activates a pH-regulated and Cd(2+)-sensitive short circuit current, characteristic properties of the ClC-2 Cl(-) channel. These data suggest that IFN-gamma activates ClC-2 channel activity in lung epithelial cells via mRNA stabilization.