title: Proteinase-activated receptor 2 activation in the airways enhances antigen-mediated airway inflammation and airway hyperresponsiveness through different pathways.
abstract: BACKGROUND
  Serine proteinases such as mast cell tryptase, trypsin-like enzymes, and certain allergens are important in the pathogenesis of asthma. These proteinases can activate the proteinase-activated receptor (PAR)-2, which has been shown to be upregulated in the airways of patients with asthma.
  
  
  OBJECTIVE
  The purpose of this study was to investigate PAR-2 activation in the airways during allergen challenge and its effects on the 2 principle features of asthma, airway inflammation and airway hyperresponsiveness (AHR).
  
  
  METHODS
  Proteinase-activated receptor 2 activating peptide SLIGRL-NH2 (PAR-2 activating peptide [ap]) or control peptide LSIGRL-NH2 (PAR-2 control peptide [cp]) was administered alone or in conjunction with ovalbumin intranasally to mice, and AHR and airway inflammation were evaluated.
  
  
  RESULTS
  PAR2ap did not induce AHR or airway inflammation in ovalbumin-sensitized mice that had not been challenged with ovalbumin. When administered with ovalbumin, PAR-2ap enhanced AHR and airway inflammation compared with ovalbumin administered alone or with PAR-2cp. The enhanced AHR persisted for 5 days, whereas the enhancement to airway inflammation dissipated. Mice administered PAR-2ap alone during the 5 days after the final antigen challenge demonstrated an additional enhancement to airway inflammation compared with the control animals. PAR-2ap administered with allergen increased TNF and IL-5 mRNA in lung tissue and IL-13 and TNF in bronchoalveolar lavage fluid.
  
  
  CONCLUSIONS
  Exogenous PAR-2 activation in parallel with allergen challenge enhances allergen-mediated AHR and airway inflammation through distinct mechanisms. PAR-2 activation can also enhance established airway inflammation even when dissociated from exposure to allergen. Therefore, PAR-2 activation may play a pathogenic role in the development of AHR and airway inflammation.
authors.affiliation: Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Cory
authors.initials: C
authors.lastname: Ebeling
authors.forename: Paul
authors.initials: P
authors.lastname: Forsythe
authors.forename: Jason
authors.initials: J
authors.lastname: Ng
authors.forename: John R
authors.initials: JR
authors.lastname: Gordon
authors.forename: Morley
authors.initials: M
authors.lastname: Hollenberg
authors.forename: Harissios
authors.initials: H
authors.lastname: Vliagoftis
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D044462:Receptors, Proteinase-Activated / Q000276:immunology* / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D009842:Oligopeptides; D012333:RNA, Messenger; D044462:Receptors, Proteinase-Activated; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin