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

Hyung Ju Cho, Jae Young Choi, Yu Mi Yang, Jeong Hee Hong, Chang-Hoon Kim, Heon Yung Gee, Hyun Jae Lee, DongMin Shin, Joo Heon Yoon

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 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 (10μg/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.

Original languageEnglish
Pages (from-to)1254-1263
Number of pages10
JournalJournal of Cellular Biochemistry
Volume109
Issue number6
DOIs
Publication statusPublished - 2010 Apr 15

Fingerprint

PAR-2 Receptor
Pyroglyphidae
Dust
Epithelium
Fluids and Secretions
Fluids
Mucous Membrane
Bridge clearances
Mucociliary Clearance
Cystic Fibrosis Transmembrane Conductance Regulator
Swine
Nose
Epithelial Cells
Proteinase-Activated Receptors
Ions
Fluorescence Spectrometry
Ion Transport
Thrombin
Short circuit currents
Allergens

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cho, Hyung Ju ; Choi, Jae Young ; Yang, Yu Mi ; Hong, Jeong Hee ; Kim, Chang-Hoon ; Gee, Heon Yung ; Lee, Hyun Jae ; Shin, DongMin ; Yoon, Joo Heon. / House dust mite extract activates apical Cl- channels through protease-activated receptor 2 in human airway epithelia. In: Journal of Cellular Biochemistry. 2010 ; Vol. 109, No. 6. pp. 1254-1263.
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House dust mite extract activates apical Cl- channels through protease-activated receptor 2 in human airway epithelia. / Cho, Hyung Ju; Choi, Jae Young; Yang, Yu Mi; Hong, Jeong Hee; Kim, Chang-Hoon; Gee, Heon Yung; Lee, Hyun Jae; Shin, DongMin; Yoon, Joo Heon.

In: Journal of Cellular Biochemistry, Vol. 109, No. 6, 15.04.2010, p. 1254-1263.

Research output: Contribution to journalArticle

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AU - Cho, Hyung Ju

AU - Choi, Jae Young

AU - Yang, Yu Mi

AU - Hong, Jeong Hee

AU - Kim, Chang-Hoon

AU - Gee, Heon Yung

AU - Lee, Hyun Jae

AU - Shin, DongMin

AU - Yoon, Joo Heon

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AB - 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 (10μg/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.

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