Proteinase‐activated receptor‐2 blockade inhibits changes seen in a chronic murine asthma model

Background Proteinase‐Activated Receptor‐2 ( PAR 2 ) is a G protein‐coupled receptor activated by serine proteinases. We have shown that PAR 2 activation in the airways is involved in the development of allergic inflammation and airway hyperresponsiveness ( AHR ) in acute murine models. We hypothesized that functional inhibition of PAR 2 prevents allergic inflammation, AHR and airway remodeling in chronic allergic airway inflammation models. Material and Methods We developed and used a 12 week model of cockroach extract ( CE )‐mediated AHR , airway inflammation and remodeling in BALB /c mice. Results Mice sensitized and challenged with CE for 12 weeks exhibit AHR , increased numbers of eosinophils in bronchoalveolar lavage ( BAL ) and increased collagen content in the lung tissue compared to saline controls. Administration of an anti‐ PAR 2 antibody, SAM ‐11, after the initial development of airway inflammation significantly inhibited all these parameters. Conclusions Our data demonstrate that PAR 2 signaling plays a key role in CE ‐induced AHR and airway inflammation/remodeling in long term models of allergic airway inflammation. Targeting PAR 2 activation may be a successful therapeutic strategy for allergic asthma.