title: Proteinase-activated receptor-2 activation participates in allergic sensitization to house dust mite allergens in a murine model.
abstract: BACKGROUND
  Many aeroallergens contain proteinase activity and are able to induce allergic sensitization when presented to mucosal surfaces. Some of these allergens activate proteinase-activated receptor-2 (PAR2 ).
  
  
  OBJECTIVE
  To determine the role of PAR2 activation in a murine house dust mite (HDM) allergy model.
  
  
  METHODS
  We sensitized and challenged PAR2 -deficient mice with HDM, and examined allergic outcomes compared to wild-type animals. To focus on the role of PAR2 in allergic sensitization, we administered a PAR2 blocking antibody to wild-type animals during the sensitization phase and examined the outcomes immediately after sensitization or following subsequent allergen challenge.
  
  
  RESULTS
  We found PAR2 -deficient mice sensitized and challenged with HDM failed to develop airway inflammation, did not produce HDM-specific IgG1 and had less IL-4 mRNA in the lungs than wild-type animals. Prevention of PAR2 activation during sensitization in wild-type mice diminished the levels of Th2 mediators, including IL-4, IL-5 and IL-13, in the lungs. Blocking PAR2 during the sensitization phase also led to decreased manifestations of allergic disease, including airway hyperresponsiveness (AHR) and airway inflammation following subsequent allergen challenge. HDM-induced proliferation of splenocytes obtained from animals sensitized in the presence of PAR2 antibody was reduced relative to those that did not receive antibody. The effect of PAR2 blockade could be transferred to naïve mice through splenic CD4(+) T cells from sensitized mice.
  
  
  CONCLUSIONS
  PAR2 activation plays a key role during the sensitization phase of our HDM allergy model, leading to increased lung cytokine production and augmented lung reactivity. PAR2 activation is a common mechanism for sensitization to a wide variety of allergens and is therefore a potential pharmacological target to prevent allergy.
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: C E
authors.initials: CE
authors.lastname: Davidson
authors.forename: M
authors.initials: M
authors.lastname: Asaduzzaman
authors.forename: N G
authors.initials: NG
authors.lastname: Arizmendi
authors.forename: D
authors.initials: D
authors.lastname: Polley
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: J R
authors.initials: JR
authors.lastname: Gordon
authors.forename: M D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: L
authors.initials: L
authors.lastname: Cameron
authors.forename: H
authors.initials: H
authors.lastname: Vliagoftis
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology*; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D044464:Receptor, PAR-2
keywords: allergic airway inflammation; allergic sensitization, CD4 lymphocytes; house dust mites; proteinase-activated receptor-2