| First Author | Amatullah H | Year | 2021 |
| Journal | Redox Biol | Volume | 38 |
| Pages | 101796 | PubMed ID | 33246293 |
| Mgi Jnum | J:330086 | Mgi Id | MGI:6762786 |
| Doi | 10.1016/j.redox.2020.101796 | Citation | Amatullah H, et al. (2021) Protective function of DJ-1/PARK7 in lipopolysaccharide and ventilator-induced acute lung injury. Redox Biol 38:101796 |
| abstractText | 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. |
