Dimethylarginine dimethylaminohydrolase 1 protects PM2.5 exposure-induced lung injury in mice by repressing inflammation and oxidative stress

作者：Junling Gao, Tong Lei, Hongyun Wang, Kai Luo, Yuanli Wang, Bingqing Cui, Zhuoran Yu, Xiaoqi Hu, Fang Zhang, Yingjie Chen, Wenjun Ding, Zhongbing Lu · 发表于：Particle and Fibre Toxicology · 年份：2022 · DOI：10.1186/s12989-022-00505-7 · 被引用次数：27 · 研究领域：Air Quality and Health Impacts、Chronic Obstructive Pulmonary Disease (COPD) Research、Climate Change and Health Impacts

Abstract Background Airborne fine particulate matter with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) pollution is associated with the prevalence of respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease. In patients with those diseases, circulating asymmetric dimethylarginine (ADMA) levels are increased, which contributes to airway nitric oxide deficiency, oxidative stress and inflammation. Overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1), an enzyme degrading ADMA, exerts protective effects in animal models. However, the impact of DDAH1/ADMA on PM 2.5 -induced lung injury has not been investigated. Methods Ddah1 −/− and DDAH1-transgenic mice, as well as their respective wild-type (WT) littermates, were exposed to either filtered air or airborne PM 2.5 (mean daily concentration ~ 50 µg/m 3 ) for 6 months through a whole-body exposure system. Mice were also acutely exposed to 10 mg/kg PM 2.5 and/or exogenous ADMA (2 mg/kg) via intratracheal instillation every other day for 2 weeks. Inflammatory response, oxidative stress and related gene expressions in the lungs were examined. In addition, RAW264.7 cells were exposed to PM 2.5 and/or ADMA and the changes in intracellular oxidative stress and inflammatory response were determined. Results Ddah1 −/− mice developed more severe lung injury than WT mice after long-term PM 2.5 exposure, which was associated with greater induction of pulmonary oxidative stress and inflammation. In ...