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*
Division of Inflammation and Infectious Diseases, Department of Microbiology,
Asthma & Allergy Research Institute and Department of Medicine, and
Department of Physiology, University of Western Australia, Nedlands, Western Australia, Australia
Epithelia from many tissues express protease-activated receptors
(PARs) that play a major role in several different physiological
processes. In this study, we examined their capacity to modulate IL-6,
IL-8, and PGE2 production in both the A459 and BEAS-2B cell
lines and primary human bronchial epithelial cells (HBECs). All three
cell types expressed PAR-1, PAR-2, PAR-3, and PAR-4, as judged by
RT-PCR and immunocytochemistry. Agonist peptides corresponding to the
nascent N termini of PAR-1, PAR-2, and PAR-4 induced the release of
cytokines from A549, BEAS-2B, and HBECs with a rank order of potency of
PAR-2 > PAR-4 > PAR-1 at 400 µM. PAR-1, PAR-2, and PAR-4
also caused the release of PGE2 from A549 and HBECs. The
PAR-3 agonist peptide was inactive in all systems tested. PAR-1, PAR-2,
or PAR-4, in combination, caused additive IL-6 release, but only the
PAR-1 and PAR-2 combination resulted in an additive IL-8 response. PAR
peptide-induced responses were accompanied by changes in intracellular
calcium ion concentrations. However, Ca2+ ion shutoff was
2-fold slower with PAR-4 than with PAR-1 or PAR-2, suggesting
differential G protein coupling. Combined, these data suggest an
important role for PAR in the modulation of inflammation in the
lung.
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E. Sokolova, Z. Grishina, F. Buhling, T. Welte, and G. Reiser Protease-activated receptor-1 in human lung fibroblasts mediates a negative feedback downregulation via prostaglandin E2 Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L793 - L802. [Abstract] [Full Text] [PDF]
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Y.C. G. Lee, D. A. Knight, K. B. Lane, D. S. Cheng, M. A. Koay, L. R. Teixeira, J. C. Nesbitt, R. C. Chambers, P. J. Thompson, and R. W. Light Activation of proteinase-activated receptor-2 in mesothelial cells induces pleural inflammation Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L734 - L740. [Abstract] [Full Text] [PDF]
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 Y. Hirota, Y. Osuga, T. Hirata, K. Koga, O. Yoshino, M. Harada, C. Morimoto, E. Nose, T. Yano, O. Tsutsumi, et al. Evidence for the Presence of Protease-Activated Receptor 2 and Its Possible Implication in Remodeling of Human Endometrium J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1662 - 1669. [Abstract] [Full Text] [PDF]
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C.-K. Yu and C.-L. Chen Activation of Mast Cells Is Essential for Development of House Dust Mite Dermatophagoides farinae-Induced Allergic Airway Inflammation in Mice J. Immunol., October 1, 2003; 171(7): 3808 - 3815. [Abstract] [Full Text] [PDF]
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L. S. Chambers, J. L. Black, Q. Ge, S. M. Carlin, W. W. Au, M. Poniris, J. Thompson, P. R. Johnson, and J. K. Burgess PAR-2 activation, PGE2, and COX-2 in human asthmatic and nonasthmatic airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L619 - L627. [Abstract] [Full Text] [PDF]
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S. Dulon, C. Cande, N. W. Bunnett, M. D. Hollenberg, M. Chignard, and D. Pidard Proteinase-Activated Receptor-2 and Human Lung Epithelial Cells: Disarming by Neutrophil Serine Proteinases Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 339 - 346. [Abstract] [Full Text] [PDF]
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M. R. D'Andrea, M. R. Saban, N.-B. Nguyen, P. Andrade-Gordon, and R. Saban Expression of Protease-Activated Receptor-1, -2, -3, and -4 in Control and Experimentally Inflamed Mouse Bladder Am. J. Pathol., March 1, 2003; 162(3): 907 - 923. [Abstract] [Full Text] [PDF]
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N. Cenac, A.-M. Coelho, C. Nguyen, S. Compton, P. Andrade-Gordon, W. K. MacNaughton, J. L. Wallace, M. D. Hollenberg, N. W. Bunnett, R. Garcia-Villar, et al. Induction of Intestinal Inflammation in Mouse by Activation of Proteinase-Activated Receptor-2 Am. J. Pathol., November 1, 2002; 161(5): 1903 - 1915. [Abstract] [Full Text] [PDF]
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N. Asokananthan, P. T. Graham, D. J. Stewart, A. J. Bakker, K. A. Eidne, P. J. Thompson, and G. A. Stewart House Dust Mite Allergens Induce Proinflammatory Cytokines from Respiratory Epithelial Cells: The Cysteine Protease Allergen, Der p 1, Activates Protease-Activated Receptor (PAR)-2 and Inactivates PAR-1 J. Immunol., October 15, 2002; 169(8): 4572 - 4578. [Abstract] [Full Text] [PDF]
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