Journal of Cellular Biochemistry

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

Authors

  • Hyung-Ju Cho,

    1. Department of Otorhinolaryngology, Hallym University College of Medicine, Seoul, South Korea
    Search for more papers by this author
  • Jae Young Choi,

    1. Department of Otorhinolaryngology, the Yonsei University College of Medicine, Seoul, South Korea
    2. Airway Mucus Institute, the Yonsei University College of Medicine, Seoul, South Korea
    3. BK 21 project, the Yonsei University College of Medicine, Seoul, South Korea
    Search for more papers by this author
  • Yu-Mi Yang,

    1. Department of Oral Biology, BK21 Project, Yonsei University College of Dentistry, Seoul, South Korea
    Search for more papers by this author
  • Jeong Hee Hong,

    1. Department of Oral Biology, BK21 Project, Yonsei University College of Dentistry, Seoul, South Korea
    Search for more papers by this author
  • Chang-Hoon Kim,

    1. Department of Otorhinolaryngology, the Yonsei University College of Medicine, Seoul, South Korea
    2. Airway Mucus Institute, the Yonsei University College of Medicine, Seoul, South Korea
    3. Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, South Korea
    Search for more papers by this author
  • Heon Young Gee,

    1. Department of Pharmacology, the Yonsei University College of Medicine, Seoul, South Korea
    Search for more papers by this author
  • Hyun Jae Lee,

    1. BK 21 project, the Yonsei University College of Medicine, Seoul, South Korea
    Search for more papers by this author
  • Dong Min Shin,

    1. Department of Oral Biology, BK21 Project, Yonsei University College of Dentistry, Seoul, South Korea
    Search for more papers by this author
  • Joo-Heon Yoon

    Corresponding author
    1. Department of Otorhinolaryngology, the Yonsei University College of Medicine, Seoul, South Korea
    2. Airway Mucus Institute, the Yonsei University College of Medicine, Seoul, South Korea
    3. BK 21 project, the Yonsei University College of Medicine, Seoul, South Korea
    4. Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, South Korea
    • Department of Otorhinolaryngology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
    Search for more papers by this author

  • Hyung-Ju Cho, Jae Young Choi and Yu-Mi Yang contributed equally to this study.

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 (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.

Ancillary