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Effects of Endocrine Disruptor Compounds, Alone or in Combination, on Human Macrophage-Like THP-1 Cell Response.

Couleau N, Falla J, Beillerot A, Battaglia E, D'Innocenzo M, Plançon S, Laval-Gilly P, Bennasroune A - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Université de Lorraine, CNRS UMR 7360, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), IUT Thionville-Yutz, Espace Cormontaigne, Yutz, France.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of EDCs alone and in combination on phagocytosis by differentiated THP-1 cells.Differentiated THP-1 cells (PMA 5 ng/ml for 48 hours) were exposed to different concentrations (0.001, 0.1, 1 and 10 μM) of BPA, DEHP, DBP, 4-OP or a combination of both for 24 hours. Culture medium was replaced by fresh medium containing 10 ng/ml of LPS for a subsequent 24 hours of incubation. Panels A and B depict confocal laser microscopy analysis of phagocytosis of FITC-latex beads by untreated differentiated THP-1 cells (A) or by differentiated THP-1 cells exposed to BPA (B). Arrows show examples of phagocytized FITC-beads. Panel C represents the effects of BPA, DEHP, DBP, 4-OP and a combination of both (BPA + DEHP, BPA + DBP, 4-OP + DEHP) on phagocytosis of latex beads by differentiated THP-1 cells. Values are means ± SD (N = 3). Each experiment has been performed three times and in triplicate. a: vs control (One-way ANOVA, Tukey post test, p<0.05).
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pone.0131428.g001: Effect of EDCs alone and in combination on phagocytosis by differentiated THP-1 cells.Differentiated THP-1 cells (PMA 5 ng/ml for 48 hours) were exposed to different concentrations (0.001, 0.1, 1 and 10 μM) of BPA, DEHP, DBP, 4-OP or a combination of both for 24 hours. Culture medium was replaced by fresh medium containing 10 ng/ml of LPS for a subsequent 24 hours of incubation. Panels A and B depict confocal laser microscopy analysis of phagocytosis of FITC-latex beads by untreated differentiated THP-1 cells (A) or by differentiated THP-1 cells exposed to BPA (B). Arrows show examples of phagocytized FITC-beads. Panel C represents the effects of BPA, DEHP, DBP, 4-OP and a combination of both (BPA + DEHP, BPA + DBP, 4-OP + DEHP) on phagocytosis of latex beads by differentiated THP-1 cells. Values are means ± SD (N = 3). Each experiment has been performed three times and in triplicate. a: vs control (One-way ANOVA, Tukey post test, p<0.05).

Mentions: The ability of differentiated THP-1 cells to phagocytize FITC-latex beads was evaluated by analyzing by CLSM THP-1 cells exposed or not to EDCs tested alone or in combination (respectively Fig 1A and 1B). Non-exposed cells showed a phagocytosis capacity of 82% (data not shown).


Effects of Endocrine Disruptor Compounds, Alone or in Combination, on Human Macrophage-Like THP-1 Cell Response.

Couleau N, Falla J, Beillerot A, Battaglia E, D'Innocenzo M, Plançon S, Laval-Gilly P, Bennasroune A - PLoS ONE (2015)

Effect of EDCs alone and in combination on phagocytosis by differentiated THP-1 cells.Differentiated THP-1 cells (PMA 5 ng/ml for 48 hours) were exposed to different concentrations (0.001, 0.1, 1 and 10 μM) of BPA, DEHP, DBP, 4-OP or a combination of both for 24 hours. Culture medium was replaced by fresh medium containing 10 ng/ml of LPS for a subsequent 24 hours of incubation. Panels A and B depict confocal laser microscopy analysis of phagocytosis of FITC-latex beads by untreated differentiated THP-1 cells (A) or by differentiated THP-1 cells exposed to BPA (B). Arrows show examples of phagocytized FITC-beads. Panel C represents the effects of BPA, DEHP, DBP, 4-OP and a combination of both (BPA + DEHP, BPA + DBP, 4-OP + DEHP) on phagocytosis of latex beads by differentiated THP-1 cells. Values are means ± SD (N = 3). Each experiment has been performed three times and in triplicate. a: vs control (One-way ANOVA, Tukey post test, p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489735&req=5

pone.0131428.g001: Effect of EDCs alone and in combination on phagocytosis by differentiated THP-1 cells.Differentiated THP-1 cells (PMA 5 ng/ml for 48 hours) were exposed to different concentrations (0.001, 0.1, 1 and 10 μM) of BPA, DEHP, DBP, 4-OP or a combination of both for 24 hours. Culture medium was replaced by fresh medium containing 10 ng/ml of LPS for a subsequent 24 hours of incubation. Panels A and B depict confocal laser microscopy analysis of phagocytosis of FITC-latex beads by untreated differentiated THP-1 cells (A) or by differentiated THP-1 cells exposed to BPA (B). Arrows show examples of phagocytized FITC-beads. Panel C represents the effects of BPA, DEHP, DBP, 4-OP and a combination of both (BPA + DEHP, BPA + DBP, 4-OP + DEHP) on phagocytosis of latex beads by differentiated THP-1 cells. Values are means ± SD (N = 3). Each experiment has been performed three times and in triplicate. a: vs control (One-way ANOVA, Tukey post test, p<0.05).
Mentions: The ability of differentiated THP-1 cells to phagocytize FITC-latex beads was evaluated by analyzing by CLSM THP-1 cells exposed or not to EDCs tested alone or in combination (respectively Fig 1A and 1B). Non-exposed cells showed a phagocytosis capacity of 82% (data not shown).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Université de Lorraine, CNRS UMR 7360, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), IUT Thionville-Yutz, Espace Cormontaigne, Yutz, France.

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.

No MeSH data available.


Related in: MedlinePlus