IPF sera-induced cellular effects were significantly blunted in cells exposed to the NADPH oxidase inhibitor diphenyleneiodonium (DPI) proving the causative role of ROS and suggesting their potential cellular source.
The key origins of oxidative stress in pulmonary fibrosis (e.g. environmental toxins, mitochondria/NADPH oxidase of inflammatory and lung target cells, and depletion of antioxidant defenses) are reviewed.
IPF fibroblasts also contained large excess of reactive oxygen species (ROS) due to the activation of an NADPH oxidase-like system, displayed higher levels of tyrosine phosphorylated proteins and were more resistant to oxidative-stress induced cell death.