Grant: Operating Grant

More than 3 million Canadians cope with a serious pulmonary disease related to inflammation. Recent reports suggest that with global warming and aging of the population, these numbers are bound to increase further. Inflammation is a complex biological response to injurious stimuli to protect and repair affected tissues. This response directs inflammatory mediators to the site of injury via increase permeability of blood vessels. Hallmarks of inflammation have been recognized since antiquity but the molecular mechanisms underlying this complex process are just becoming apparent. Chronic inflammation is the result of prolonged inflammation, which cannot fully resolve itself and leads to progressive tissue destruction. The mainstay treatment for many inflammatory diseases is steroids. These are highly effective in the treatment of most cases of asthma, but a small number are steroid-resistant. Other chronic inflammatory diseases like chronic obstructive pulmonary disease and cystic fibrosis are largely resistant to the therapeutic effect of steroids, while patients are still susceptible to their side effects. Therefore alternative treatments are required for these diseases. The main objective of this research program is to investigate the molecular mechanisms underlying pulmonary chronic inflammation and identify novel strategy to re-establish the balance of inflammation. We propose to achieve this by obtaining a clearer understanding of key signals emanating from cells lining the airways in response to bacterial infection. It is becoming apparent that when cells are infected and die they release factors that can further augment inflammation. This research proposal will investigate such a factor, called IL-33, to understand its role when released from epithelial cells that have died because of bacterial infections. This proposal aims to determine whether or not targeting IL-33 would be beneficial in decreasing the burden of inflammation of Cystic Fibrosis patients.