Interaction of Mite Allergens Der P3 and Der P9 with Protease-Activated Receptor-2 Expressed by Lung Epithelial Cells
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TLDR
The results suggest that Der p 3 and Der p9 may induce a nonallergic inflammatory response in the airways through the release of proinflammatory cytokines from the bronchial epithelium and that this effect is at least in part mediated by PAR-2.Abstract:
The respiratory epithelium represents the first barrier encountered by airborne Ags. Two major dust mite Ags, Der p3 and Der p9, are serine proteases that may activate lung epithelial cells by interaction with the protease-activated receptor 2 (PAR-2). In this study both Der p3 and Der p9 cleaved the peptide corresponding to the N terminus of PAR-2 at the activation site. Both Ags sequentially stimulated phosphoinositide hydrolysis, transient cytosolic Ca2+ mobilization, and release of GM-CSF and eotaxin in human pulmonary epithelial cells. These responses were similar to those observed with trypsin and a specific PAR-2 agonist and were related to the serine protease activity of Der p3 and Der p9. Cell exposure to the Ags resulted in a refractory period, indicating that a PAR had been cleaved. Partial desensitization to Der p3 and Der p9 by the PAR-2 agonist suggested that PAR-2 was one target of the Ags. However, PAR-2 was not the only target, because the PAR-2 agonist caused less desensitization to Der p3 and Der p9 than did trypsin. A phospholipase C inhibitor prevented the cytokine-releasing effect of the PAR-2 agonist and abolished or reduced (>70%) the cytokine-releasing effects of Der p3 and Der p9. Our results suggest that Der p 3 and Der p9 may induce a nonallergic inflammatory response in the airways through the release of proinflammatory cytokines from the bronchial epithelium and that this effect is at least in part mediated by PAR-2.read more
Citations
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Journal ArticleDOI
Protease-Activated Receptors: Contribution to Physiology and Disease
TL;DR: Major future challenges will be to understand the role of proteases and PARs in physiological control mechanisms and human diseases and to develop selective agonists and antagonists that can be used to probe function and treat disease.
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EAACI Molecular Allergology User's Guide.
Paolo Maria Matricardi,Jörg Kleine-Tebbe,Hans Jürgen Hoffmann,Rudolf Valenta,Christiane Hilger,Stephanie Hofmaier,Rob C. Aalberse,Ioana Agache,Riccardo Asero,Barbara Ballmer-Weber,Domingo Barber,Kirsten Beyer,Tilo Biedermann,M. B. Bilò,Simon Blank,Barbara Bohle,Philipp P. Bosshard,Heimo Breiteneder,Helen A. Brough,Luis Caraballo,J-C Caubet,Reto Crameri,Janet M. Davies,Nikolaos Douladiris,M. Ebisawa,Philippe Eigenmann,Montserrat Fernandez-Rivas,Fatima Ferreira,Gabriele Gadermaier,Martin Glatz,Robert G. Hamilton,Thomas Hawranek,P W Hellings,Karin Hoffmann-Sommergruber,Thilo Jakob,Uta Jappe,Marek Jutel,Sandip D. Kamath,Edward F. Knol,Peter Korošec,Annette Kuehn,Gideon Lack,Gideon Lack,Andreas L. Lopata,Mika J. Mäkelä,Martine Morisset,Verena Niederberger,Anna Nowak-Wegrzyn,Nikolaos G. Papadopoulos,Elide A. Pastorello,Gabrielle Pauli,Thomas A.E. Platts-Mills,Daniela Posa,Lars K. Poulsen,Monika Raulf,Joaquín Sastre,Enrico Scala,Johannes Schmid,Peter Schmid-Grendelmeier,M. van Hage,R. van Ree,Stefan Vieths,Richard W. Weber,Magnus Wickman,Antonella Muraro,Markus Ollert +65 more
TL;DR: The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) as mentioned in this paper provides comprehensive information on important allergens and describes the diagnostic options using component-resolved diagnosis (CRD).
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Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response.
Martin Steinhoff,Jörg Buddenkotte,Victoria M. Shpacovitch,Anke Rattenholl,Corinna Moormann,Nathalie Vergnolle,Thomas A. Luger,Morley D. Hollenberg +7 more
TL;DR: The activation of a new subfamily of G protein-coupled receptors, termed proteinase-activated receptors (PARs), necessitates a paradigm shift in thinking about hormone action, to include proteinases as key modulators of biological function.
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International Union of Pharmacology. XXVIII. Proteinase-Activated Receptors
TL;DR: This article summarizes the experiments leading to the pharmacological characterization and cloning of the four PAR family members and provides a rationale for their designation by the acronym “PAR”, and discusses the newly appreciated roles of proteinases as signaling molecules that can act as either functional agonists or antagonists.
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Continuous Exposure to House Dust Mite Elicits Chronic Airway Inflammation and Structural Remodeling
Jill R. Johnson,Ryan E. Wiley,Ramzi Fattouh,Filip K. Swirski,Beata U. Gajewska,Anthony J. Coyle,Jose-Carlos Gutierrez-Ramos,Russ Ellis,Mark D. Inman,Manel Jordana +9 more
TL;DR: It is observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly, and these responses were studied for up to 9 weeks after cessation of HDM exposure.
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