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8:2 fluorotelomer alcohol inhibited proliferation and disturbed the expression of pro-inflammatory cytokines and antigen-presenting genes in murine macrophages

Author:
Kong, Baida, Wang, Xia, He, Bingnan, Wei, Lai, Zhu, Jianbo, Jin, Yuanxiang, Fu, Zhengwei
Source:
Chemosphere 2019 v.219 pp. 1052-1060
ISSN:
0045-6535
Subject:
alcohols, cell cycle checkpoints, cell lines, cell proliferation, cell viability, gene expression, gene expression regulation, genes, hepatotoxicity, immunotoxicity, industry, interleukin-6, macrophages, messenger RNA, mice, nephrotoxicity, organofluorine compounds, polymers, reactive oxygen species, risk, surfactants, tumor necrosis factor-alpha
Abstract:
Fluorotelomer alcohols (FTOHs, F(CF2)nCH2CH2OH) are members of per- and polyfluoroalkyl substances (PFASs) and are increasingly used in surfactant and polymer industries. FTOHs pose hepatotoxicity, nephrotoxicity and endocrine-disrupting risks. Nevertheless, there is limited research on the immunotoxic effects of FTOHs. In this study, we examined the immunotoxicity of 8:2 FTOH (n = 8) on murine macrophage cell line RAW 264.7. The results showed that 8:2 FTOH exposure reduced cell viability in dose- and time-dependent manners, inhibited cell proliferation and caused cell cycle arrest. Exposure to 8:2 FTOH downregulated the mRNA expression of some cell cycle-related genes, including Cdk4, Ccnd1, Ccne1, and p53, but also upregulated the mRNA expression of other cell cycle related genes, including Ccna2, p21, and p27. Additionally, exposure to 8:2 FTOH under unstimulated and LPS-stimulated conditions downregulated the mRNA expression of pro-inflammatory genes, including Il1b, Il6, Cxcl1, and Tnfa, and secreted levels of IL-6 and TNF-α. Treatment with 8:2 FTOH upregulated the mRNA expression of antigen-presenting-related genes, including H2-K1, H2-Ka, Cd80, and Cd86. The abovementioned immunotoxic effects caused by 8:2 FTOH in RAW 264.7 cells were partially or completely blocked by co-treatment with hydralazine hydrochloride (Hyd), a reactive carbonyl species (RCS) scavenger. However, exposure to 8:2 FTOH did not exhibit any effects on intracellular reactive oxygen species (ROS) level with or without LPS stimulation. Taken together, these results suggest that 8:2 FTOH may have immunotoxic effects on macrophages and RCS may underlie the responsible mechanism. The present study aids in understanding the health risks caused by FTOHs.
Agid:
6257861