Hyung-Ju Cho, Jae Young Choi and Yu-Mi Yang contributed equally to this study.
House dust mite extract activates apical Cl− channels through protease-activated receptor 2 in human airway epithelia†
Article first published online: 23 FEB 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 109, Issue 6, pages 1254–1263, 15 April 2010
How to Cite
Cho, H.-J., Choi, J. Y., Yang, Y.-M., Hong, J. H., Kim, C.-H., Gee, H. Y., Lee, H. J., Shin, D. M. and Yoon, J.-H. (2010), House dust mite extract activates apical Cl− channels through protease-activated receptor 2 in human airway epithelia. J. Cell. Biochem., 109: 1254–1263. doi: 10.1002/jcb.22511
- Issue published online: 26 MAR 2010
- Article first published online: 23 FEB 2010
- Manuscript Accepted: 30 DEC 2009
- Manuscript Received: 22 AUG 2009
- Korea Healthcare technology R&D Project
- Ministry of Health and Welfare
- Republic of Korea. Grant Number: A08-0047
- house dust mites;
- ion channel;
- protease-activated receptors;
- nasal epithelium
Adequate fluid secretion from airway mucosa is essential for maintaining mucociliary clearance, and fluid hypersecretion is a prominent feature of inflammatory airway diseases such as allergic rhinitis. House dust mite extract (HDM) has been reported to activate protease-activated receptors (PARs), which play various roles in airway epithelia. However, the role of HDM in regulating ion transporters and fluid secretion has not been investigated. We examined the effect of HDM on ion transport in human primary nasal epithelial cells. The Ca2+-sensitive dye Fura2-AM was used to determine intracellular Ca2+ concentration ([Ca2+]i) by means of spectrofluorometry in human normal nasal epithelial cells (NHNE). Short-circuit current (Isc) was measured using Ussing chambers. Fluid secretion from porcine airway mucosa was observed by optical measurement. HDM extract (10 µg/Ml) effectively cleaved the PAR-2 peptide and induced an increase of [Ca2+]i that was abolished by desensitization with trypsin, but not with thrombin. Apical application of HDM-induced Isc sensitive to both a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor and a Ca2+-activated Cl− channel (CaCC) inhibitor. HDM extract also stimulated fluid secretion from porcine airway mucosa. HDM extract activated PAR-2 and apical Cl− secretion via CaCC and CFTR, and HDM-induced fluid secretion in porcine airway mucosa. Our results suggest a role for PAR-2 in mucociliary clearance and fluid hypersecretion of airway mucosa in response to air-borne allergens such as HDM. J. Cell. Biochem. 109: 1254–1263, 2010. © 2010 Wiley-Liss, Inc.