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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 | | Language: | ENG. | | Date: | 13-5-2008 | | Journal: | American journal of respiratory cell and molecular biology
(1535-4989)
| | Release: | Am J Respir Cell Mol Biol. 12 May 2008 | |
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Abstract:
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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 (IP3) 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/IP3-dependent Ca(2+) signaling in human airway epithelial cells.
| | Copyright: | American journal of respiratory cell and molecular biology
Department of Oral Biology, Brain Korea 21 Project, Yonsei University College of Dentistry, Center for Natural Defense System, Seoul, 120-752, Korea, Republic of. | | Full text: | | | |
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