2. Academic Validation
  3. Bisphenol F promotes the secretion of pro-inflammatory cytokines in macrophages by enhanced glycolysis through PI3K-AKT signaling pathway

Bisphenol F promotes the secretion of pro-inflammatory cytokines in macrophages by enhanced glycolysis through PI3K-AKT signaling pathway

  • Toxicol Lett. 2021 Oct 10;350:30-39. doi: 10.1016/j.toxlet.2021.06.011.
Wenfeng Zhang 1,  Li Li 2,  Huiling Chen 3,  Yanchao Zhang 4,  Zihan Zhang 5,  Zeheng Lin 6,  Mingjie Shi 7,  Wei Zhang 8,  Xing Li 9,  Zhi Tang 10,  Yungang Liu 11,  Lianxian Guo 12,  Ming Shi 13
Affiliations

Affiliations

  • 1 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 2 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 3 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 4 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 5 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 6 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 7 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 8 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 9 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 10 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 11 Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong Province, China. Electronic address: [email protected].
  • 12 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
  • 13 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China; Liaobu Hospital, Guangdong Medical University, Dongguan, 523808, Guangdong Province, China. Electronic address: [email protected].
PMID: 34147605 DOI: 10.1016/j.toxlet.2021.06.011
Abstract

Bisphenol F (BPF) is a member of endocrine disrupting chemicals (EDCs). As a substitute of bisphenol A (BPA), BPF is widely used in various consumer products, leading to an increased risk of people's exposure. However, there are few studies on the immunotoxicity and mechanism of BPF. This study aimed to investigate the effect of BPF on the secretion of pro-inflammatory cytokines by macrophages and explore its mechanism. In our study, RAW264.7 macrophages were treated with different concentrations of BPF (0, 5, 10 and 20 μM) for 24 h. The results showed that the secretion of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) and the production of lactate were increased in a dose-dependent manner. BPFalso led to the activation of the PI3K-AKT signaling pathway. After pretreatment with glycolysis inhibitor (2-DG) and exposure to BPF (20 μM), the secretion of pro-inflammatory cytokines induced by BPF was inhibited. PI3K Inhibitor (LY294002) and Estrogen Receptor (ER) antagonist (ICI 182,780) could also inhibit the above effects induced by BPF (20 μM). In conclusion, our results suggested that BPF can enhance glycolysis through ER mediated PI3K-AKT signaling pathway, and the enhanced glycolysis further promoted the secretion of pro-inflammatory cytokines. Our research provides basic data for future studies on bisphenol exposure and immunotoxicity.

Keywords

Bisphenol F; Glycolysis; Immunotoxicity; Inflammation; Macrophage.

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