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Chu, S. et al.

Chu, Blaisdell, Bamford, Ferro,

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

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.[1]

References

Interferon-gamma regulates ClC-2 chloride channel in lung epithelial cells. Chu, S., Blaisdell, C.J., Bamford, P., Ferro, T.J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]

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