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

Fluorotelomer alcohols (FTOHs, F(CF 2 ) n CH 2 CH 2 OH) 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.