Protective function of DJ-1/PARK7 in lipopolysaccharide and ventilator-induced acute lung injury
Hajera Amatullah, Tatiana Maron‐Gutierrez, Yuexin Shan, Sahil Gupta, James N. Tsoporis, Amir K. Varkouhi, Ana Paula Teixeira Monteiro, Xiaolin He, Jun Yin, John C. Marshall, Patrícia R. M. Rocco, Haibo Zhang, Wolfgang M. Kuebler, Claúdia C. dos Santos
Abstract
Oxidative stress is considered one of the early underlying contributors of acute lung injury (ALI) and ventilator-induced lung injury (VILI). DJ-1, also known as PARK7, has a well-established role as an antioxidant. We have previously shown maintaining oxidative balance via the ATF3-Nrf2 axis was important in protection from ALI. Here, we exclusively characterize the role of DJ-1 in sterile LPS-induced ALI and VILI. DJ-1 protein expression was increased after LPS treatment in human epithelial and endothelial cell lines and lungs of wild-type mice. DJ-1 deficient mice exhibited greater susceptibility to LPS-induced acute lung injury as demonstrated by increased cellular infiltration, augmented levels of pulmonary cytokines, enhanced ROS levels and oxidized by-products, increased pulmonary edema and cell death. In a two-hit model of LPS and mechanical ventilation (MV), DJ-1 deficient mice displayed enhanced susceptibility to inflammation and lung injury. Collectively, these results identify DJ-1 as a negative regulator of ROS and inflammation, and suggest its expression protects from sterile lung injury driven by high oxidative stress.