Effects of Endocrine Disruptor Compounds, Alone or in Combination, on Human Macrophage-Like THP-1 Cell Response

PLoS One. 2015 Jul 2;10(7):e0131428. doi: 10.1371/journal.pone.0131428. eCollection 2015.


The aim of the present study was to evaluate the immunological effects on human macrophages of four endocrine disruptor compounds (EDCs) using the differentiated human THP-1 cell line as a model. We studied first the effects of these EDCs, including Bisphenol A (BPA), di-ethylhexyl-phthalate (DEHP), dibutyl phthalate (DBP) and 4-tert-octylphenol (4-OP), either alone or in combination, on cytokine secretion, and phagocytosis. We then determined whether or not these effects were mediated by estrogen receptors via MAPK pathways. It was found that all four EDCs studied reduced strongly the phagocytosis of the differentiated THP-1 cells and that several of these EDCs disturbed also TNF-α, IL-1 β and IL-8 cytokine secretions. Furthermore, relative to control treatment, decreased ERK 1/2 phosphorylation was always associated with EDCs treatments-either alone or in certain combinations (at 0.1 μM for each condition). Lastly, as treatments by an estrogen receptor antagonist suppressed the negative effects on ERK 1/2 phosphorylation observed in cells treated either alone with BPA, DEHP, 4-OP or with the combined treatment of BPA and DEHP, we suggested that estrogen receptor-dependent pathway is involved in mediating the effects of EDCs on human immune system. Altogether, these results advocate that EDCs can disturb human immune response at very low concentrations.

MeSH terms

  • Benzhydryl Compounds / pharmacology*
  • Cell Line
  • Dibutyl Phthalate / pharmacology*
  • Diethylhexyl Phthalate / pharmacology*
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / pharmacology*
  • Gene Expression Regulation
  • Humans
  • Interleukin-1beta / agonists
  • Interleukin-1beta / metabolism
  • Interleukin-8 / agonists
  • Interleukin-8 / metabolism
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phagocytosis / drug effects
  • Phenols / pharmacology*
  • Phosphorylation / drug effects
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / agonists
  • Tumor Necrosis Factor-alpha / metabolism


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Interleukin-1beta
  • Interleukin-8
  • Phenols
  • Receptors, Estrogen
  • Tumor Necrosis Factor-alpha
  • Dibutyl Phthalate
  • Diethylhexyl Phthalate
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • 4-tert-octylphenol
  • bisphenol A

Grants and funding

The authors received no specific funding for this work.