Environmentally relevant level of PFDA exacerbates intestinal inflammation by activating the cGAS/STING/NF-κB signaling pathway.

Autor: Cui Z; Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Yuan X; Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Wang Y; Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Liu Z; Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Fei X; Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Chen K; Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Shen HM; Faculty of Health Sciences, Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Macau., Wu Y; Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences, Hangzhou, China. Electronic address: georgewu@zju.edu.cn., Xia D; Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou, China. Electronic address: dxia@zju.edu.cn.
Jazyk: angličtina
Zdroj: The Science of the total environment [Sci Total Environ] 2024 Dec 01; Vol. 954, pp. 176786. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1016/j.scitotenv.2024.176786
Abstrakt: As a constituent of the Per- and Polyfluoroalkyl Substances (PFAS) family, perfluorodecanoic acid (PFDA) is ubiquitous in the environment and enters the human body through environmental exposure, the food chain, and other pathways, resulting in various toxic effects. Previous population-based studies have suggested a correlation between PFDA exposure and inflammation. However, the evidence is still limited, and the potential mechanisms underlying this correlation remain to be further elucidated. In our study, we observed that exposure to internal doses of PFDA significantly promoted macrophage inflammation through in vitro assays. Utilizing RNA-seq screening and molecular experiments, we identified that environmentally relevant concentration of PFDA promote inflammation mainly by activating non-canonical cGAS/STING/NF-κB pathways in vitro. Finally, we confirmed in the typical mouse inflammatory bowel disease (IBD) model that PFDA could exacerbate intestinal inflammation in a cGAS dependent manner. In conclusion, our research firstly demonstrated that even at environmentally relevant concentrations, PFDA could promote the progression of intestinal inflammation primarily through the cGAS/STING/NF-κB pathway, revealing the potential risk associated with PFDA exposure and providing theoretical evidence for its management.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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