NLRP3 inflammasome-mediated disruption of mitochondrial homeostasis in alveolar macrophages contributes to ozone-induced acute lung inflammatory injury
Ozone (O<sub>3</sub>), a prevalent atmospheric pollutant, can induce lung injury. However, the molecular mechanisms of O<sub>3</sub>-induced acute lung inflammatory injury remain unclear. In this study, we investigate the...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
China Science Publishing & Media Ltd.
2024-10-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024171 |
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| Summary: | Ozone (O<sub>3</sub>), a prevalent atmospheric pollutant, can induce lung injury. However, the molecular mechanisms of O<sub>3</sub>-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<sub>3</sub>-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<sub>3</sub>-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<sub>3</sub>-exposed mice, the number of mitochondria, mtROS, and fission-related protein DRP1 are increased, but the levels of Na<sup>+</sup>‐K<sup>+</sup>‐ATPase, fusion-related protein OPA1, biogenesis-related protein NRF1 and mtDNA are significantly decreased. Compared with that in O<sub>3</sub>-exposed WT mice, lung inflammation is attenuated, especially the indicators of mitochondrial homeostatic imbalance in AMs, which are alleviated in NLRP3<sup>‒/‒</sup> and Caspase-1<sup>‒/‒</sup> mice after O<sub>3</sub> exposure. These findings indicate that the NLRP3 inflammasome-mediated imbalance in mitochondrial homeostasis in AMs contributes to O<sub>3</sub>-induced acute lung inflammatory injury. This study may provide a new target for the prevention of lung inflammation induced by O<sub>3</sub>. |
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| ISSN: | 1672-9145 |