House dust mite extract activates apical Cl(-) channels through protease-activated receptor 2 in human airway epithelia.
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.
Cho
Hyung-Ju
HJ
Department of Otorhinolaryngology, Hallym University College of Medicine, Seoul, South Korea.
Choi
Jae Young
JY
Yang
Yu-Mi
YM
Hong
Jeong Hee
JH
Kim
Chang-Hoon
CH
Gee
Heon Young
HY
Lee
Hyun Jae
HJ
Shin
Dong Min
DM
Yoon
Joo-Heon
JH
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018408:Patch-Clamp Techniques; D039981:Pyroglyphidae / Q000737:chemistry*; D044464:Receptor, PAR-2 / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism
D000485:Allergens; D018118:Chloride Channels; D044464:Receptor, PAR-2; D002118:Calcium