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
- 15 October 2002
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 169 (8), 4572-4578
- https://doi.org/10.4049/jimmunol.169.8.4572
Abstract
In previous studies, we demonstrated that allergenic house dust mite proteases are potent inducers of proinflammatory cytokines from the respiratory epithelium, although the precise mechanisms involved were unclear. In this study, we investigated whether this was achieved through activation of protease-activated receptor (PAR)-1 or -2. Pretreatment of A549 respiratory epithelial cells with the clinically important cysteine protease allergen, Der p 1, ablated subsequent PAR-1, but not PAR-2 agonist peptide-induced IL-6 and IL-8 release. HeLa cells transfected with the plasmid coding for PAR-2, in contrast to PAR-1, released significant concentration of IL-6 after exposure to Der p 1. Exposure of HeLa cells transfected with either PAR-1/enhanced yellow fusion protein or PAR-2/enhanced yellow fusion protein to Der p 1 caused receptor internalization in the latter cells only, as judged by confocal microscopy with re-expression of the receptor within 120-min postenzyme exposure. Der p 1-induced cytokine release from both A549 and transfected HeLa cells was accompanied by changes in intracellular Ca2+ concentrations. Desensitization studies showed that Der p 1 pretreatment of the A549 cells resulted in the abolition of both trypsin- and PAR-2 agonist peptide-induced Ca2+ release, but not that induced by subsequent exposure to either thrombin or PAR-1 agonist peptide. These data indicate for the first time that the house dust mite allergen Der p 1-induced cytokine release from respiratory epithelial cells is, in part, mediated by activation of PAR-2, but not PAR-1.Keywords
This publication has 37 references indexed in Scilit:
- The Role of Domestic AllergensPublished by Wiley ,2007
- Protease-activated receptors in human airways: Upregulation of PAR-2 in respiratory epithelium from patients with asthmaJournal of Allergy and Clinical Immunology, 2001
- Protease-activated receptors and the airway epitheliumClinical & Experimental Allergy Reviews, 2001
- Protease-activated Receptor-1 Down-regulationJournal of Biological Chemistry, 2000
- Ligand Cross-reactivity within the Protease-activated Receptor FamilyPublished by Elsevier BV ,1996
- The House Dust Mite AllergenDer p1 Catalytically Inactivates α1-Antitrypsin by Specific Reactive Centre Loop Cleavage: A Mechanism That Promotes Airway Inflammation and AsthmaBiochemical and Biophysical Research Communications, 1996
- Thrombin Receptor Activating Mutations: ALTERATION OF AN EXTRACELLULAR AGONIST RECOGNITION DOMAIN CAUSES CONSTITUTIVE SIGNALINGPublished by Elsevier BV ,1996
- Proteolysis of the Human Platelet and Endothelial Cell Thrombin Receptor by Neutrophil-derived Cathepsin GPublished by Elsevier BV ,1995
- Effect of mite allergen on permeability of bronchial mucosaThe Lancet, 1990
- Isolation and Characterization of Two Allergens from Dermatophagoides farinaeInternational Archives of Allergy and Immunology, 1986