title: Bisphenol A suppresses Th1-type immune response in human peripheral blood mononuclear cells in vitro.
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.
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria; Receptor Biology Group, Inflammation, Repair and Development Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Gostner
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Raggl
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Becker
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Überall
authors.affiliation: Central Institute of Blood Transfusion and Immunology, University Hospital, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Schennach
authors.affiliation: Receptor Biology Group, Inflammation, Repair and Development Section, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Pease
authors.affiliation: Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria. Electronic address: dietmar.fuchs@i-med.ac.at.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D001559:Benzhydryl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D019798:Neopterin / Q000276:immunology / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014364:Tryptophan / Q000276:immunology / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D007371:Interferon-gamma; D016328:NF-kappa B; D019798:Neopterin; D010636:Phenols; D010835:Phytohemagglutinins; D014364:Tryptophan; C576710:IDO1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Human PBMC; Indoleamine 2,3-dioxygenase; Neopterin; Tryptophan