Bisphenol A suppresses Th1-type immune response in human peripheral blood mononuclear cells in vitro

Immunol Lett. 2015 Dec;168(2):285-92. doi: 10.1016/j.imlet.2015.10.006. Epub 2015 Oct 22.

Abstract

Bisphenol A (BPA) is a widely used plasticizer, which came into focus because of its genotoxic and sensitizing potential. Besides its toxic properties, BPA is also well-known for its antioxidant chemical properties. This in vitro study investigated the interference of BPA with interferon-γ (IFN-γ)-induced tryptophan breakdown and neopterin production in human peripheral blood mononuclear cells (PBMC). The pro-inflammatory cytokine IFN-γ induces the conversion of the essential amino acid tryptophan into kynurenine via the enzyme indoleamine-2,3-dioxygenase (IDO-1). In parallel, GTP-cyclohydrolase produces neopterin, a marker of immune activation. A model system of phytohaemagglutinin (PHA)-stimulated PBMC was used to assess potential immunomodulatory properties of BPA. Treatment of cells with BPA [12.5-200μM] resulted in a significant and dose-dependent suppression of mitogen-induced tryptophan breakdown and neopterin formation along with a decrease of IFN-γ levels. Similar but less pronounced effects were observed in unstimulated cells. We postulate that the inhibitory effects of BPA on both T-cell activation and IDO-1 activity that we describe here may be critical for immune surveillance and is likely to influence T helper (Th) type 1/Th2 balance. Such immunosuppressive effects likely contribute to counteract inflammation. Further studies are required to address the in vivo relevance our in vitro findings.

Keywords: Bisphenol A; Human PBMC; Indoleamine 2,3-dioxygenase; Neopterin; Tryptophan.

MeSH terms

  • Benzhydryl Compounds / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Neopterin / immunology
  • Neopterin / metabolism
  • Phenols / pharmacology*
  • Phytohemagglutinins / pharmacology
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Tryptophan / immunology
  • Tryptophan / metabolism

Substances

  • Benzhydryl Compounds
  • Cytokines
  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Inflammation Mediators
  • NF-kappa B
  • Phenols
  • Phytohemagglutinins
  • Neopterin
  • Interferon-gamma
  • Tryptophan
  • bisphenol A