Asbestosis is a debilitating interstitial lung disease caused by the inhalation of asbestos fibers and characterized by inflammation and fibrosis of alveolar interstitium. The pathogenesis of asbestosis is not fully understood, but reactive oxygen species (ROS) are thought to play a central role. Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the lung in other interstitial lung diseases but has not been studied in asbestos-mediated disease. The hypothesis of this proposal is that EC-SOD protects against asbestos-mediated lung injury by preventing oxidative damage and matrix metalloproteinase (MMP) activation. These studies will utilize biochemical and histological analyses to study the presence of EC-SOD in the lungs of asbestos- or control-treated mice. In addition, EC-SOD knockout and transgenic overexpressing mice will be treated with asbestos to determine if the presence of this antioxidant affects disease severity. Finally, experiments will examine whether the presence of EC-SOD affects activation of latent MMPs since these proteases can become activated by ROS and are known to contribute to disease progression in other models of pulmonary fibrosis. ? ?
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