1. Academic Validation
  2. Estrogen receptor-regulated SOCS3 modulation via JAK2/STAT3 pathway is involved in BPF-induced M1 polarization of macrophages

Estrogen receptor-regulated SOCS3 modulation via JAK2/STAT3 pathway is involved in BPF-induced M1 polarization of macrophages

  • Toxicology. 2020 Mar 30;433-434:152404. doi: 10.1016/j.tox.2020.152404.
Mingjie Shi 1 Zeheng Lin 1 Lihe Ye 2 Xinlin Chen 1 Wenfeng Zhang 1 Zihan Zhang 1 Fei Luo 1 Yungang Liu 3 Ming Shi 4
Affiliations

Affiliations

  • 1 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, 523808, Dongguan, China.
  • 2 Department of Occupational Health Determination, Dongguan Sixth People's Hospital, 523808, Dongguan, China.
  • 3 Department of Toxicology, School of Public Health, Southern Medical University, 510515, Guangzhou, China.
  • 4 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, 523808, Dongguan, China. Electronic address: [email protected].
Abstract

As an alternative to bisphenol A (BPA), bisphenol F (BPF) has been increasingly used in manufacturing various consumer products. Exposured to BPF may lead to imbalanced immune homeostasis, yet the underlying mechanisms have not been fully elucidated. The present study was aimed to investigate the effects of BPF on macrophages and the underlying mechanism in regard to its association with Estrogen Receptor (ER), janus kinase 2/signal transducer and activator of transcription 3/suppressor of cytokine signaling 3 (JAK2/STAT3/SOCS3) pathway. In this study, after treatment of RAW264.7 macrophages with BPF (0, 5, 10, 20 μM), the macrophage M1 polarization was promoted, and the gene expression of M1 functional markers and pro-inflammatory cytokines was upregulated, which suggested the involvement of a vicious circle associated with chronic inflammation. Moreover, BPF facilitated SOCS3 expression in the cells in a dose-dependent manner, via activation of the JAK2/STAT3 signaling pathway, which may promote the transcription of many pro-inflammatory factors. Additionally, the above effects of BPF were blocked by either JAK2/STAT3 Inhibitor AG490 (10 μM) or ER antagonist ICI 182,780 (10 μM). Taken together, the results of this study indicate that BPF promotes macrophage polarization toward pro-inflammatory M1 subtype, through activation of the ER-JAK2/STAT3/SOCS3 signaling pathway. Our finding may provide a new insight into the link between bisphenol exposure and immune dysfunction.

Keywords

Bisphenol F (BPF); Estrogen receptor; JAK2/STAT3 pathway; Macrophage polarization; SOCS3.

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