Oxidative stress and pulmonary fibrosis

Abstract

Interstitial lung diseases are characterized by pathologic involvement of the alveolar parenchyma that frequently leads to irreversible and progressive fibrosis. The pathogenesis of these fibrotic diseases, like idiopathic pulmonary fibrosis (IPF), is thought to involve abnormal alveolar reepithelialization, myofibroblast differentiation/activation, dysregulated matrix remodeling, inflammation, and oxidative stress. Indeed, increased levels of markers of oxidative stress and decreased antioxidant activity have been found in lungs of patients with IPF. This oxidative imbalance (i.e., increased reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) or decreased antioxidants) can directly damage the epithelium and lead to degradation of the extracellular matrix in the lungs. This causes irreversible injury that results in the deposition of scar tissue and a further loss of antioxidant enzymes. In addition, ROS and RNS can also contribute to the pathogenesis of pulmonary fibrosis by altering the expression of other fibrotic mediators, such as transforming growth factor-β, proteases, and antiproteases. Overall, oxidants, like ROS and RNS, may modulate the development of pulmonary fibrosis, and therefore, antioxidant enzymes may serve as potential targets for drug therapies to treat these debilitating diseases.