Protease-Activated Receptor-2 blockade inhibits changes seen in a chronic murine asthma model

Abstract

Proteinase-Activated Receptor-2 (PAR₂) is a G protein-coupled receptor activated by serine proteinases. We have shown that PAR₂ activation in the airways is involved in the development of allergic inflammation and airway hyperresponsiveness (AHR) in acute murine models. We hypothesize that functional inhibition of PAR₂ prevents allergic inflammation, AHR and airway remodeling in chronic allergic airway inflammation models. We developed a 12 week model of cockroach extract (CE)-mediated AHR, airway inflammation and remodeling in BALB/c. These mice 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-PAR₂ antibody, SAM-11, after the initial development of airway inflammation significantly inhibited all these parameters. Our data demonstrate that PAR₂ signaling plays a key role in CE-induced AHR and airway inflammation/remodeling and that targeting PAR₂ activation may be a successful therapeutic strategy for allergic asthma.

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