mtDNA amplifies beryllium sulfate-induced inflammatory responses via the cGAS-STING pathway in 16HBE cells.

Autor: Liu X; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China., Jiang T; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China., Jin H; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China., Yan C; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China., Tong Y; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China., Ding J; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China., Li Y; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China., Huang L; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China., Zhang Z; Department of Preventive Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.; Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang, China.
Jazyk: angličtina
Zdroj: Journal of applied toxicology : JAT [J Appl Toxicol] 2024 Sep; Vol. 44 (9), pp. 1403-1415. Date of Electronic Publication: 2024 May 22.
DOI: 10.1002/jat.4631
Abstrakt: Beryllium sulfate (BeSO 4 ) can cause inflammation through the mechanism, which has not been elucidated. Mitochondrial DNA (mtDNA) is a key contributor of inflammation. With mitochondrial damage, released mtDNA can bind to specific receptors (e.g., cGAS) and then activate related pathway to promote inflammatory responses. To investigate the mechanism of mtDNA in BeSO 4 -induced inflammatory response in 16HBE cells, we established the BeSO 4 -induced 16HBE cell inflammation model and the ethidium bromide (EB)-induced ρ 0 16HBE cell model to detect the mtDNA content, oxidative stress-related markers, mitochondrial membrane potential, the expression of the cGAS-STING pathway, and inflammation-related factors. Our results showed that BeSO 4 caused oxidative stress, decline of mitochondrial membrane potential, and the release of mtDNA into the cytoplasm of 16HBE cells. In addition, BeSO 4 induced inflammation in 16HBE cells by activating the cGAS-STING pathway. Furthermore, mtDNA deletion inhibited the expression of cGAS-STING pathway, IL-10, TNF-α, and IFN-β. This study revealed a novel mechanism of BeSO 4 -induced inflammation in 16HBE cells, which contributes to the understanding of the molecular mechanism of beryllium and its compounds-induced toxicity.
(© 2024 John Wiley & Sons, Ltd.)
Databáze: MEDLINE