Interferon-???? regulates ClC-2 chloride channel in lung epithelial cells

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• 作者：Chu ; Shijian ; Blaisdell ; Carol J. ; Bamford ; Penelope ; Ferro ; Thomas J.
• 关键词：Lung epithelium ; Ion channel ; Interferon-???? ; Gene expression ; mRNA ; Promoter
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：November 5, 2004
• 年：2004
• 卷：324
• 期：1
• 页码：31-39
• 全文大小：799 K

文摘

Epithelial Cl^aaa channels mediate Cl^aaa and fluid secretion in the lung. In cystic fibrosis, aberrant Cl^aaa secretion is one of the major causes for lung fluid imbalance. Regulation of Cl^aaa channels is therefore an important issue in the lung. IFN-aa regulates Na⁺ and Cl^aaa channels and fluid transport in the lung, but the mechanisms involved in these regulations are not clear. In expression studies, we found that IFN-aa 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-aa did not activate the promoter. Instead, IFN-aa significantly increased ClC-2 transcript stability. Using Ussing chamber experiments, we demonstrate that IFN-aa activates a pH-regulated and Cd²⁺-sensitive short circuit current, characteristic properties of the ClC-2 Cl^aaa channel. These data suggest that IFN-aa activates ClC-2 channel activity in lung epithelial cells via mRNA stabilization.