1. Parkin deficiency exacerbates particulate matter-induced injury by enhancing airway epithelial necroptosis.
- Author
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Lin Y, Quan M, Wang X, Miao W, Xu H, He B, Liu B, Zhang Y, Chen Y, Zhou B, Xu M, Dong L, Jin X, Lou Z, Zhang JS, and Chen C
- Subjects
- Animals, Mice, Air Pollutants toxicity, Epithelial Cells drug effects, Inflammation, Cell Line, Necroptosis drug effects, Particulate Matter toxicity, Mice, Inbred C57BL, Ubiquitin-Protein Ligases metabolism, Ubiquitin-Protein Ligases genetics
- Abstract
Exposure to fine particulate matter (PM) disrupts the function of airway epithelial barriers causing cellular stress and damage. However, the precise mechanisms underlying PM-induced cellular injury and the associated molecular pathways remain incompletely understood. In this study, we used intratracheal instillation of PM in C57BL6 mice and PM treatment of the BEAS-2B cell line as in vivo and in vitro models, respectively, to simulate PM-induced cellular damage and inflammation. We collected lung tissues and bronchoalveolar lavage fluids to assess histopathological changes, necroptosis, and airway inflammation. Our findings reveal that PM exposure induces necroptosis in mouse airway epithelial cells. Importantly, concurrent administration of a receptor interacting protein kinases 3 (RIPK3) inhibitor or the deletion of the necroptosis effector mixed-lineage kinase domain-like protein (MLKL) effectively attenuated PM-induced airway inflammation. PM exposure dose-dependently induces the expression of Parkin, an E3 ligase we recently reported to play a pivotal role in necroptosis through regulating necrosome formation. Significantly, deletion of endogenous Parkin exacerbates inflammation by enhancing epithelial necroptosis. These results indicate that PM-induced Parkin expression plays a crucial role in suppressing epithelial necroptosis, thereby reducing airway inflammation. Overall, these findings offer valuable mechanistic insights into PM-induced airway injury and identify a potential target for clinical intervention., Competing Interests: Declaration of competing interest The authors declare that they have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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