title: DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells.
abstract: Recent studies have demonstrated that compounds inducing pro-inflammatory cytokines enhance AhR expression. The aim of this study was 2-fold: (1) to determine if two pro-inflammatory compounds, dichlorodiphenyldichloroethylene (DDE) and 2,2',4,4',5,5'-hexa-chlorobiphenyl (PCB 153), independently affect AhR gene expression in peripheral blood mononuclear cells (PBMC); and (2) if affected, to determine whether the mechanism involved was due to AhR activation or to a pro-inflammatory effect of the chemicals. PBMC isolated from healthy individuals were incubated in the presence of DDE (10 µg/ml) and PCB 153 (20 ng/ml) over time and AhR and CYP1A1 expression was assessed with a real-time PCR technique. The results indicated there was over-expression of the AhR mRNA in PBMC when the cells were treated with DDE and PCB 153. No changes in expression levels of CYP1A1 mRNA were found. Importantly, when the cells were exposed to DDE and PCB 153 in the presence of an antagonist of tumor necrosis factor (TNF)-α, the over-expression of AhR was abolished; as expected, the expression of CYP1A1 was unaffected. In conclusion, these studies demonstrated for the first time an increment of AhR expression "in vitro" in PBMC treated with two pro-inflammatory environmental pollutants, DDE and PCB153. Moreover, the over-expression of AhR was dependent of TNFα induced by DDE and PCB 153 and was independent of AhR activation.
authors.affiliation: Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí , San Luis Potosí , México .
authors.forename: Octavio
authors.initials: O
authors.lastname: Gaspar-Ramírez
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pérez-Vázquez
authors.forename: Mariana
authors.initials: M
authors.lastname: Salgado-Bustamante
authors.forename: Roberto
authors.initials: R
authors.lastname: González-Amaro
authors.forename: Berenice
authors.initials: B
authors.lastname: Hernandez-Castro
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Pérez-Maldonado
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D018836:Inflammation Mediators / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: D019138:Antibodies, Blocking; D004785:Environmental Pollutants; D018836:Inflammation Mediators; D018336:Receptors, Aryl Hydrocarbon; D014409:Tumor Necrosis Factor-alpha; D003633:Dichlorodiphenyl Dichloroethylene; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
keywords: AhR; Aryl hydrocarbon receptor; CYP1A1; DDE; PCB 153; TNFα