1. Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction
- Author
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Aili Simaiti, Peilin Yu, Wei Yang, Xiaobo Cai, Shunni Dong, Lin-Hua Jiang, Jianhong Luo, Xin Yang, Jin Li, Xinqiang Zhu, Binyang Du, and Mingxiang Wang
- Subjects
0301 basic medicine ,Surface Properties ,Health, Toxicology and Mutagenesis ,lcsh:Industrial hygiene. Industrial welfare ,TRPM Cation Channels ,Inflammation ,02 engineering and technology ,Lung injury ,Toxicology ,medicine.disease_cause ,Mice ,03 medical and health sciences ,lcsh:RA1190-1270 ,Lysosome ,Autophagy ,medicine ,Animals ,TRPM2 ,Viability assay ,Particle Size ,Lysosomal impairment ,lcsh:Toxicology. Poisons ,Inhalation Exposure ,Lung ,business.industry ,Research ,Pneumonia ,General Medicine ,Silicon Dioxide ,021001 nanoscience & nanotechnology ,Autophagy dysfunction ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Pulmonary inflammation ,Cancer research ,Nanoparticles ,Poly(ADP-ribose) Polymerases ,medicine.symptom ,Lysosomes ,Reactive Oxygen Species ,0210 nano-technology ,business ,lcsh:HD7260-7780.8 ,ROS/PARP/TRPM2 signaling ,Oxidative stress ,Signal Transduction - Abstract
Background Wide applications of nanoparticles (NPs) have raised increasing concerns about safety to humans. Oxidative stress and inflammation are extensively investigated as mechanisms for NPs-induced toxicity. Autophagy and lysosomal dysfunction are emerging molecular mechanisms. Inhalation is one of the main pathways of exposing humans to NPs, which has been reported to induce severe pulmonary inflammation. However, the underlying mechanisms and, more specifically, the interplays of above-mentioned mechanisms in NPs-induced pulmonary inflammation are still largely obscure. Considered that NPs exposure in modern society is often unavoidable, it is highly desirable to develop effective strategies that could help to prevent nanomaterials-induced pulmonary inflammation. Results Pulmonary inflammation induced by intratracheal instillation of silica nanoparticles (SiNPs) in C57BL/6 mice was prevented by PJ34, a poly (ADP-ribose) polymerase (PARP) inhibitor. In human lung bronchial epithelial (BEAS-2B) cells, exposure to SiNPs reduced cell viability, and induced ROS generation, impairment in lysosome function and autophagic flux. Inhibition of ROS generation, PARP and TRPM2 channel suppressed SiNPs-induced lysosome impairment and autophagy dysfunction and consequent inflammatory responses. Consistently, SiNPs-induced pulmonary inflammation was prevented in TRPM2 deficient mice. Conclusion The ROS/PARP/TRPM2 signaling is critical in SiNPs-induced pulmonary inflammation, providing novel mechanistic insights into NPs-induced lung injury. Our study identifies TRPM2 channel as a new target for the development of preventive and therapeutic strategies to mitigate nanomaterials-induced lung inflammation. Graphical abstract
- Published
- 2020
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