No abstract

No abstract

As a viable substitute for bisphenol A (BPA), BPF has been widely used in the plastic industry and daily consumer goods, resulting in its detection in humans at a comparable concentration. Evidence reveals that BPF and BPA may have similar toxic effects due to their similar structures. However, there is less information about BPF and its latent implications on the immune system, which is associated with many disorders. In this study, the in vitro toxicity of BPF on RAW264.7 macrophages was explored. The cells were treated with different concentrations of BPF (5, 10, 20, 50, 100, and 200 μM), the cell viability and apoptosis were detected, the gene expression profile was analyzed by whole-transcriptome sequencing, and the mRNA levels were detected by qRT-PCR. The results showed a high concentration of BPF could significantly reduce the survival rate of RAW264.7 macrophages. Although the medium concentration (20–50 μM) of BPF seemed to have no impact on the cell activity of macrophages, it caused the occurrence of apoptosis. The results of differential transcription showed that compared with the control group, 121 genes were upregulated and 82 genes were downregulated in the BPF group. The significantly changed gene functions were mainly concentrated in cell cycle, phagosome, lysosome, and antigen processing and presentation. These findings provide valuable information for correctly understanding the immunotoxicity risk of BPF and may help to improve the hazard identification of bisphenol compounds.

Triphenyl phosphate (TPHP) is one of the most widely used organic phosphorus flame retardants and is ubiquitous in the environment. Studies have been reported that TPHP may lead to obesity, neurotoxicity and reproductive toxicity, but its impact on the immune system is almost blank. The present study was aimed to investigate the potential immunotoxicity of TPHP on macrophages and its underlying mechanism. The results demonstrated for the first time that TPHP (12.5, 25, and 50 μM)‐induced F4/80+CD11c+ phenotype of RAW 264.7 macrophages, accompanied by increased mRNA levels of inflammatory mediators, antigen‐presenting genes (Cd80, Cd86, and H2‐Aa), and significantly enhanced the phagocytosis of macrophage. Meanwhile, TPHP increased the expression of Toll‐like receptor 4 (TLR4), and its co‐receptor CD14, leading to significant activation of the downstream ERK/NF‐κB pathway. However, co‐exposure of cells to TAK‐242, a TLR4 inhibitor, suppressed TPHP‐induced F4/80+CD11c+ phenotype, and down‐regulated inflammatory mediators and antigen‐presentation related genes, via blocked the TLR4/ERK/NF‐κB pathway. Taken together, our results suggested that TPHP could induce macrophage dysfunction through activating TLR4‐mediated ERK/NF‐κB signaling pathway, and it may be the potential reason for health‐threatening consequences.