Expression of pro-inflammatory cytokines and mediators induced by Bisphenol A via ERK-NFκB and JAK1/2-STAT3 pathways in macrophages

Environ Toxicol. 2019 Apr;34(4):486-494. doi: 10.1002/tox.22702. Epub 2019 Jan 4.


Macrophages not only play an important role in the innate immune response but also participate in many inflammatory and infectious diseases including asthma, diabetes, obesity, cardiovascular diseases, and cancers. Bisphenol A (BPA) is the most commonly used component for plastic products. However, BPA is an endocrine disruptor for mammals and participates in several inflammatory and infectious diseases. Up until now, there are no researches demonstrated the potential role of BPA in macrophage activation and its relative mechanism. BPA promoted the generation of proinflammatory cytokines IL-1β, IL-6, and TNFα in a concentration-dependent manner (P < 0.05). BPA was identified to increase the expression of proinflammatory mediators NO and PGE2, and its upstream factors iNOS, COX2, and cPLA2 in a concentration-dependent manner (P < 0.05). Phosphorylation and nuclear translocation of NF-κB p65 were significantly induced by BPA via IκB degradation (P < 0.05). In addition, phosphorylation of ERK significantly induced by BPA at a concentration which was less than that for phosphorylation of p38 MAPK and JNK (P < 0.05). Furthermore, phosphorylation of STAT3 significantly induced by BPA at a concentration lower than that for phosphorylation of STAT1 (P < 0.05). Phosphorylation of JAK1 and JAK2 was also significantly induced by BPA in a concentration-dependent manner (P < 0.05).

Keywords: ERK-NFκB; JAK1/2-STAT3; bisphenol A; macrophages; proinflammatory mediators.

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Cytokines / genetics*
  • Dose-Response Relationship, Drug
  • Janus Kinase 1 / drug effects*
  • Janus Kinase 2 / drug effects*
  • MAP Kinase Signaling System / drug effects*
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Phenols / toxicity*
  • Phosphorylation
  • RAW 264.7 Cells
  • STAT3 Transcription Factor / metabolism*
  • Transcription Factor RelA / metabolism*


  • Benzhydryl Compounds
  • Cytokines
  • Phenols
  • STAT3 Transcription Factor
  • Transcription Factor RelA
  • Janus Kinase 1
  • Janus Kinase 2
  • bisphenol A