Peroxiredoxin 1 inhibits lipopolysaccharide-induced oxidative stress in lung tissue by regulating P38/JNK signaling pathway.

OBJECTIVE To investigate the potential role of peroxiredoxin 1 in lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice and the possible mechanism. MATERIALS AND METHODS Male Prdx1 knockout mice (Prdx1 (-/-)) and C57BL/6 wild-type mice with the same genetic background were used in this experiment. Primary culture of peritoneal macrophages was performed to measure the level of reactive oxygen species. The acute lung injury (ALI) model was induced by intraperitoneal injection of LPS (5 mg/kg). The mice were sacrificed at 6 h and 24 h after the treatment. The pathological changes of the lungs, wet/dry ratio and protein levels in bronchoalveolar lavage fluid (BALF) were measured. The levels of hydrogen peroxide (H2O2), malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant capacity (TAOC) were also measured in lung tissue homogenates. RESULTS Our study found that the knockout of Prdx1 gene significantly increased the ROS content in mouse macrophages after LPS treatment, and the lung wet/dry ratio and BALF protein concentration were also increased, indicating the increased lung pathological damage. Prdx1 gene knockout significantly reduced the antioxidant capacity of lung tissue, increased its oxidative capacity and oxidative stress in lung. Prdx1 knockdown also significantly increased p38 mitogen-activated protein kinases (P38) and c-Jun N-terminal protein kinase (JNK) protein phosphorylation levels, leading to the activation of P38/JNK signaling pathway. CONCLUSIONS Prdx1 knockout can aggravate the oxidative stress and lung injury by increasing the level of Reactive Oxygen Species (ROS), and also activate P38/JNK signaling pathway. Therefore, the anti-oxidative of Prdx1 reduced LPS-induced acute lung injury in mice.