Grant: Chair: GlaxoSmithKline Partnered - Operating Component

Asthma affects more than 3 million Canadian, causing significant morbidity and high cost for the health care system. Although we have some excellent medications to treat airway inflammation, the majority of asthmatics remain poorly controlled. Developing a treatment strategy that minimizes discomfort and side effects will be of immense significance. Asthma is characterized by airway hyper-responsiveness, which is an exaggerated response of the airways to irritating stimuli, and airway inflammation, which is evident by the presence of large numbers of eosinophils in the airways and excessive mucus secretion. We have shown in mouse models that airway inflammation is dependent on the presence of specific molecules called serine proteinases. These molecules can activate a receptor on the surface of the airway epithelium called Proteinase Activated Receptor-2 (PAR-2). We will study the functions of this receptor in allergic airway inflammation using mouse models of asthma and airway epithelial cells isolated from human airway. We will also study PAR-2 expression on a type of blood cells called monocytes. Our data indicate that reagents that block PAR-2 activation have tremendous potential to become new therapeutic options for asthma. Our data also show that measuring the levels of PAR-2 in blood monocytes may be useful in predicting the severity of disease.