DDE and PCB 153 independently induce aryl hydrocarbon receptor (AhR) expression in peripheral blood mononuclear cells
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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. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.
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AhR; Aryl hydrocarbon receptor; CYP1A1; DDE; PCB 153; TNFα 1,1 dichloro 2,2 bis(4 chlorophenyl)ethylene; 2,2',4,4',5,5' hexachlorobiphenyl; aromatic hydrocarbon receptor; cytochrome P450 1A1; messenger RNA; tumor necrosis factor alpha; 1,1 dichloro 2,2 bis(4 chlorophenyl)ethylene; 2,4,5,2',4',5'-hexachlorobiphenyl; aromatic hydrocarbon receptor; autacoid; blocking antibody; cytochrome P450 1A1; pollutant; polychlorinated biphenyl; tumor necrosis factor; Article; controlled study; gene expression; gene overexpression; human; human cell; in vitro study; inflammation; normal human; peripheral blood mononuclear cell; pollutant; priority journal; real time polymerase chain reaction; adult; cell culture; drug effects; genetics; immunology; metabolism; mononuclear cell; physiology; toxicity; upregulation; young adult; Adult; Antibodies, Blocking; Cells, Cultured; Cytochrome P-450 CYP1A1; Dichlorodiphenyl Dichloroethylene; Environmental Pollutants; Humans; Inflammation Mediators; Leukocytes, Mononuclear; Polychlorinated Biphenyls; Receptors, Aryl Hydrocarbon; Tumor Necrosis Factor-alpha; Up-Regulation; Young Adult
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