title: Effects of Endocrine Disruptor Compounds, Alone or in Combination, on Human Macrophage-Like THP-1 Cell Response.
abstract: 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.
authors.affiliation: Université de Lorraine, CNRS UMR 7360, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), IUT Thionville-Yutz, Espace Cormontaigne, Yutz, France.
authors.forename: N
authors.initials: N
authors.lastname: Couleau
authors.affiliation: Université de Lorraine, CNRS UMR 7360, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), IUT Thionville-Yutz, Espace Cormontaigne, Yutz, France.
authors.forename: J
authors.initials: J
authors.lastname: Falla
authors.affiliation: IUT Thionville-Yutz, Impasse Alfred Kastler Espace Cormontaigne, Yutz, France.
authors.forename: A
authors.initials: A
authors.lastname: Beillerot
authors.affiliation: Université de Lorraine, CNRS UMR 7360, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Campus Bridoux-8, Metz, France.
authors.forename: E
authors.initials: E
authors.lastname: Battaglia
authors.affiliation: IUT Thionville-Yutz, Impasse Alfred Kastler Espace Cormontaigne, Yutz, France.
authors.forename: M
authors.initials: M
authors.lastname: D'Innocenzo
authors.affiliation: Calcium Signaling and Inflammation Group, Life Sciences Research Unit, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: S
authors.initials: S
authors.lastname: Plançon
authors.affiliation: Université de Lorraine, CNRS UMR 7360, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), IUT Thionville-Yutz, Espace Cormontaigne, Yutz, France.
authors.forename: P
authors.initials: P
authors.lastname: Laval-Gilly
authors.affiliation: Université de Lorraine, CNRS UMR 7360, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), IUT Thionville-Yutz, Espace Cormontaigne, Yutz, France.
authors.forename: A
authors.initials: A
authors.lastname: Bennasroune
mesh_terms: D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002460:Cell Line; D003993:Dibutyl Phthalate / Q000494:pharmacology*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000819:agonists / Q000378:metabolism; D016209:Interleukin-8 / Q000819:agonists / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003993:Dibutyl Phthalate; D004051:Diethylhexyl Phthalate; D052244:Endocrine Disruptors; D053583:Interleukin-1beta; D016209:Interleukin-8; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010636:Phenols; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; C535150:MAPK1 protein, human; C105260:4-tert-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds