| Autor: |
Miao X; Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China., Li X; Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China., Ma P; Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China., Li M; Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China., Jiang Y; Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China., Wang P; Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China., Zhou X; Department of Pulmonary Medicine, Chest Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450000, China., Wang L; Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China., Shang P; Key Laboratory of Tobacco Chemistry, Zhengzhou Tobacco Research Institute, CNTC, Zhengzhou 450001, China., Zhang Q; Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China., Feng F; Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China. |
| Abstrakt: |
Ozone (O 3 ), a prevalent atmospheric pollutant, can induce lung injury. However, the molecular mechanisms of O 3 -induced acute lung inflammatory injury remain unclear. In this study, we investigate the abnormal changes in and molecular mechanism of mitochondrial homeostasis in alveolar macrophages (AMs) in O 3 -induced acute lung inflammatory injury mice. Mitochondria and mitochondrial reactive oxygen species (mtROS) are labeled with Mito-Tracker® Deep Red and MitoSOX Red, respectively. Mitochondrial DNA (mtDNA) in AMs from the bronchoalveolar lavage fluid (BALF) is detected via real-time PCR, and the expressions of mitochondrial fusion/fission-related and biogenesis-related proteins in AMs are determined via immunofluorescence staining. Our data show that in O 3 -induced acute lung inflammatory injury mice, the number of AMs and the protein expression of the NLRP3 inflammasome complex in the lung tissue are increased. In AMs from O 3 -exposed mice, the number of mitochondria, mtROS, and fission-related protein DRP1 are increased, but the levels of Na + -K + -ATPase, fusion-related protein OPA1, biogenesis-related protein NRF1 and mtDNA are significantly decreased. Compared with that in O 3 -exposed WT mice, lung inflammation is attenuated, especially the indicators of mitochondrial homeostatic imbalance in AMs, which are alleviated in NLRP3 ‒/‒ and Caspase-1 ‒/‒ mice after O 3 exposure. These findings indicate that the NLRP3 inflammasome-mediated imbalance in mitochondrial homeostasis in AMs contributes to O 3 -induced acute lung inflammatory injury. This study may provide a new target for the prevention of lung inflammation induced by O 3 . |
