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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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M. O. Judex and B. M. Mueller Plasminogen Activation/Plasmin in Rheumatoid Arthritis: Matrix Degradation and More Am. J. Pathol., March 1, 2005; 166(3): 645 - 647. [Abstract] [Full Text] [PDF]
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 M. Steinhoff, J. Buddenkotte, V. Shpacovitch, A. Rattenholl, C. Moormann, N. Vergnolle, T. A. Luger, and M. D. Hollenberg Proteinase-Activated Receptors: Transducers of Proteinase-Mediated Signaling in Inflammation and Immune Response Endocr. Rev., February 1, 2005; 26(1): 1 - 43. [Abstract] [Full Text] [PDF]
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 G. Busch, I. Seitz, B. Steppich, S. Hess, R. Eckl, A. Schomig, and I. Ott Coagulation Factor Xa Stimulates Interleukin-8 Release in Endothelial Cells and Mononuclear Leukocytes: Implications in Acute Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 461 - 466. [Abstract] [Full Text] [PDF]
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 M. J. Flick, X. Du, and J. L. Degen Fibrin(ogen)-{alpha}M{beta}2 Interactions Regulate Leukocyte Function and Innate Immunity In Vivo Experimental Biology and Medicine, December 1, 2004; 229(11): 1105 - 1110. [Abstract] [Full Text] [PDF]
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N. Tanaka, T. Morita, A. Nezu, A. Tanimura, I. Mizoguchi, and Y. Tojyo Signaling Mechanisms Involved in Protease-Activated Receptor-1-Mediated Interleukin-6 Production by Human Gingival Fibroblasts J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 778 - 786. [Abstract] [Full Text] [PDF]
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L. Hu, M. Lee, W. Campbell, R. Perez-Soler, and S. Karpatkin Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis Blood, November 1, 2004; 104(9): 2746 - 2751. [Abstract] [Full Text] [PDF]
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A. Oshiro, H. Otani, Y. Yagi, S. Fukuhara, and C. Inagaki Protease-Activated Receptor-2-Mediated Inhibition for Ca2+ Response to Lipopolysaccharide in Guinea Pig Tracheal Epithelial Cells Am. J. Respir. Cell Mol. Biol., June 1, 2004; 30(6): 886 - 892. [Abstract] [Full Text] [PDF]
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G. M. Hjortoe, L. C. Petersen, T. Albrektsen, B. B. Sorensen, P. L. Norby, S. K. Mandal, U. R. Pendurthi, and L. V. M. Rao Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration Blood, April 15, 2004; 103(8): 3029 - 3037. [Abstract] [Full Text] [PDF]
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M. Chokki, S. Yamamura, H. Eguchi, T. Masegi, H. Horiuchi, H. Tanabe, T. Kamimura, and S. Yasuoka Human Airway Trypsin-Like Protease Increases Mucin Gene Expression in Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 2004; 30(4): 470 - 478. [Abstract] [Full Text] [PDF]
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C. J. Lockwood, P. Kumar, G. Krikun, S. Kadner, P. Dubon, H. Critchley, and F. Schatz Effects of Thrombin, Hypoxia, and Steroids on Interleukin-8 Expression in Decidualized Human Endometrial Stromal Cells: Implications for Long-Term Progestin-Only Contraceptive-Induced Bleeding J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1467 - 1475. [Abstract] [Full Text] [PDF]
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M. Terada, E. A. B. Kelly, and N. N. Jarjour Increased Thrombin Activity after Allergen Challenge: A Potential Link to Airway Remodeling? Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 373 - 377. [Abstract] [Full Text] [PDF]
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R. S. Lan, G. A. Stewart, R. G. Goldie, and P. J. Henry Altered expression and in vivo lung function of protease-activated receptors during influenza A virus infection in mice Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L388 - L398. [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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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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