title: House dust mite extract activates apical Cl(-) channels through protease-activated receptor 2 in human airway epithelia.
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.
authors.affiliation: Department of Otorhinolaryngology, Hallym University College of Medicine, Seoul, South Korea.
authors.forename: Hyung-Ju
authors.initials: HJ
authors.lastname: Cho
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Yang
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Hong
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Kim
authors.forename: Heon Young
authors.initials: HY
authors.lastname: Gee
authors.forename: Hyun Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Shin
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
mesh_terms: 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
chemical_list: D000485:Allergens; D018118:Chloride Channels; D044464:Receptor, PAR-2; D002118:Calcium