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Chitinase activates protease-activated receptor-2 in human airway epithelial cells

Authors
 Jeong Hee Hong  ;  Jung Yeon Hong  ;  Boryung Park  ;  Syng-Ill Lee  ;  Jeong Taeg Seo  ;  Kyu-Earn Kim  ;  Myung Hyun Sohn  ;  Dong Min Shin 
Citation
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol.39(5) : 530-535, 2008 
Journal Title
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 
ISSN
 1044-1549 
Issue Date
2008
MeSH
Bronchi/cytology* ; Bronchi/metabolism ; Calcium/metabolism ; Calcium Signaling ; Cells, Cultured ; Chitinases/metabolism* ; Epithelial Cells/metabolism* ; Humans ; Interleukin-8/biosynthesis ; Kinetics ; Receptor, PAR-2/genetics ; Receptor, PAR-2/metabolism* ; Streptomyces griseus/enzymology* ; Substrate Specificity
Keywords
chitinase ; protease-activated receptor-2 ; calcium signaling ; human airway epithelial cells
Abstract
Mammalian chitinase released by airway epithelia is thought to be an important mediator of disease manifestation in an experimental model of asthma. However, the intracellular signaling mechanisms engaged by exogenous chitinase in human airway epithelial cells are unknown. Here, we investigated the direct effects of exogenous chitinase from Streptomyces griseus on Ca(2+) signaling in human airway epithelial cells. Spectrofluorometry was used to measure intracellular Ca(2+) concentration ([Ca(2+)](i)) in fura-2-AM-loaded cells. S. griseus chitinase induced dose-dependent [Ca(2+)](i) increases in normal human bronchial epithelial cells and promoted [Ca(2+)](i) oscillations in H292 cells. Chitinase-induced [Ca(2+)](i) oscillations were independent of extracellular Ca(2+), suggesting that the observed [Ca(2+)](i) increases were due to Ca(2+) release from intracellular stores. Accordingly, after depleting endoplasmic reticulum (ER) Ca(2+) with the ER Ca(2+) ATPase inhibitor, thapsigargin, chitinase-mediated [Ca(2+)](i) increases were abolished. Treatment with the phospholipase C (PLC) inhibitor U73122 or the 1, 4, 5-trisinositolphosphate (IP(3)) receptor inhibitor 2-APB attenuated chitinase-induced [Ca(2+)](i) increases. Desensitization of protease-activated receptor-2 (PAR-2) by repetitive agonist stimulation or siRNA-mediated PAR-2 knock-down revealed that chitinase-mediated [Ca(2+)](i) increases were exclusively mediated by PAR-2 activation. Finally, chitinase was found to cleave a model peptide representing the cleavage site of PAR-2 and enhanced IL-8 production. These results indicate that exogenous chitinase is a potent proteolytic activator of PAR-2 that can directly induce PLC/IP(3)-dependent Ca(2+) signaling in human airway epithelial cells.
Full Text
http://www.atsjournals.org/doi/abs/10.1165/rcmb.2007-0410OC
DOI
10.1165/rcmb.2007-0410OC
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Kyu Earn(김규언)
Park, Bo Ryung(박보령)
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Lee, Syng Ill(이승일)
Hong, Jung Yeon(홍정연) ORCID logo https://orcid.org/0000-0003-0406-9956
Hong, Jeong Hee(홍정희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107551
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