Grant: Operating Grant

Chronic inflammation such as that seen in asthma results in local events in lungs that compromise lung function. These include the accumulation of inflammatory cells such as eosinophils, and increases in tissue deposition (also termed matrix remodelling). Common allergens such as house mite and ragweed pollen, known to drive symptoms in allergy-induced asthma, can induce asthma-like inflammation in mouse models when introduced through the airway. The control of the inflammatory response involves numerous molecules, however we hypothesize that the hormone-like molecules called gp130 cytokines play a crucial role in the development of the lung pathology. We believe that one of these cytokines in particular, called Oncostatin M, is up-regulated in asthma and interacts with cells in synergistic fashion with other molecules important in immunity. We believe that this causes increased symptoms and pathology of the lungs. We will use approaches that examine responses in gene knockout mice and that examine in vitro responses of cells of the airway including human smooth muscle cells and lung fibroblasts. We predict that these studies will demonstrate the importance of gp130 cytokines in models of asthma, and thus point to new approaches in the study and treatment of human allergic asthmatic disease.