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House dust mite extract activates apical Cl(-) channels through protease-activated receptor 2 in human airway epithelia

Authors
 Hyung-Ju Cho  ;  Jae Young Choi  ;  Yu-Mi Yang  ;  Jeong Hee Hong  ;  Chang-Hoon Kim  ;  Heon Young Gee  ;  Hyun Jae Lee  ;  Dong Min Shin  ;  Joo-Heon Yoon 
Citation
 JOURNAL OF CELLULAR BIOCHEMISTRY, Vol.109(6) : 1254-1263, 2010 
Journal Title
 JOURNAL OF CELLULAR BIOCHEMISTRY 
ISSN
 0730-2312 
Issue Date
2010
MeSH
Allergens/pharmacology* ; Animals ; Blotting, Western ; Calcium/metabolism ; Cell Line ; Cells, Cultured ; Chloride Channels/drug effects* ; Epithelial Cells/cytology ; Epithelial Cells/drug effects* ; Epithelial Cells/metabolism* ; Humans ; Patch-Clamp Techniques ; Pyroglyphidae/chemistry* ; Receptor, PAR-2/metabolism* ; Respiratory Mucosa/cytology* ; Reverse Transcriptase Polymerase Chain Reaction ; Rhinitis/metabolism ; Rhinitis, Allergic, Seasonal/metabolism
Keywords
HOUSE DUST MITES ; SECRETION ; ION CHANNEL ; PROTEASE-ACTIVATED RECEPTORS ; NASAL EPIT HELIUM
Abstract
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 Ca(2+)-sensitive dye Fura2-AM was used to determine intracellular Ca(2+) concentration ([Ca(2+)](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 microg/Ml) effectively cleaved the PAR-2 peptide and induced an increase of [Ca(2+)](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 Ca(2+)-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.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/jcb.22511/abstract
DOI
10.1002/jcb.22511
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Yoon, Joo Heon(윤주헌)
Lee, Hyun Jae(이현재)
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
Hong, Jeong Hee(홍정희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100852
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