NADPH oxidase

NADPH oxidase

Role of NADPH Oxidase in Lung Ischemia-Reperfusion Injury

PI:  Victor Laubach, PhD


Previous studies from our lab suggest that reactive oxygen species (ROS) production plays an important role in lung IR injury. The potential enzymatic sources of ROS after IR include NADPH oxidase, nitric oxide synthase, xanthine oxidase and the mitochondrial respiratory chain. During hypoxia or ischemia, it has been shown that pulmonary epithelial or endothelial cell-derived ROS from NADPH oxidase is a crucial factor in mediating inflammation and tissue injury. We are using p47phox-/- mice (deficient in p47phox subunit of NADPH oxidase), and apocynin, a specific NADPH oxidase inhibitor, to test the hypothesis that a mechanism of CXCL1 generation in response to IL-17 and TNF-alpha after lung IR entails NADPH oxidase activation. Data so far suggests that IL-17 and TNF-alpha synergystically mediate CXCL1 production by alveolar type II epithelial cells after IR, via an NADPH oxidase-dependent mechanism, to induce neutrophil infiltration and lung IR injury. This is outlined below:

Pathway_TNF_IL-17