Channelpedia

PubMed 17426222


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClCa1 , ClvC4



Title: Niflumic acid and AG-1478 reduce cigarette smoke-induced mucin synthesis: the role of hCLCA1.

Authors: Ahmed E Hegab, Tohru Sakamoto, Akihiro Nomura, Yukio Ishii, Yuko Morishima, Takashi Iizuka, Takumi Kiwamoto, Yosuke Matsuno, Shinsuke Homma, Kiyohisa Sekizawa

Journal, date & volume: Chest, 2007 Apr , 131, 1149-56

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17426222


Abstract
Cigarette smoke induces bronchial mucus secretion. However, the mechanism of this induction is still unidentified. In this study, we investigated the role of the putative calcium-activated chloride channel 1 (CLCA1) and its blocker, niflumic acid, in cigarette smoke-induced mucin synthesis both in vivo and in vitro.Sprague-Dawley rats were exposed to cigarette smoke for 4 weeks. The CLCA1, epidermal growth factor receptor (EGFR), and MUC5AC expressions were increased in the trachea and lung tissues. Goblet-cell hyperplasia with marked mucin staining was detected in the tracheal and bronchial epithelium. In the human bronchial epithelial cell line NCI-H292, cigarette smoke solution also induced mucin production as well as the RNA and protein expressions of CLCA1, EGFR, and MUC5AC. Both in vivo and in vitro, the induction of MUC5AC and mucin synthesis were inhibited by niflumic acid, and/or a selective EGFR tyrosine kinase inhibitor, AG-1478. Niflumic acid also blocked the epidermal growth factor-induced MUC5AC and mucin staining in the NCI-H292 cell line.Both EGFR and niflumic acid-sensitive chloride channels (probably CLCA1) are dependently affecting the mucin production as a part of a single complex signaling pathway. CLCA1 may be a key signaling member that can be targeted with pharmacologic interventions to treat mucus hypersecretion.