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Bisphenol A Does Not Mimic Estrogen in the Promotion of the In Vitro Response of Murine Dendritic Cells to Toll-Like Receptor Ligands

Sex hormones affect immune responses and might promote autoimmunity. Endocrine disrupting chemicals such as bisphenol A (BPA) may mimic their immune effects. Conventional dendritic cells (cDCs) are pivotal initiators of immune responses upon activation by danger signals coming from pathogens or dist...

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Autores principales: Chakhtoura, Marita, Sriram, Uma, Heayn, Michelle, Wonsidler, Joshua, Doyle, Christopher, Dinnall, Joudy-Ann, Gallucci, Stefania, Roberts, Rebecca A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547709/
https://www.ncbi.nlm.nih.gov/pubmed/28811679
http://dx.doi.org/10.1155/2017/2034348
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author Chakhtoura, Marita
Sriram, Uma
Heayn, Michelle
Wonsidler, Joshua
Doyle, Christopher
Dinnall, Joudy-Ann
Gallucci, Stefania
Roberts, Rebecca A.
author_facet Chakhtoura, Marita
Sriram, Uma
Heayn, Michelle
Wonsidler, Joshua
Doyle, Christopher
Dinnall, Joudy-Ann
Gallucci, Stefania
Roberts, Rebecca A.
author_sort Chakhtoura, Marita
collection PubMed
description Sex hormones affect immune responses and might promote autoimmunity. Endocrine disrupting chemicals such as bisphenol A (BPA) may mimic their immune effects. Conventional dendritic cells (cDCs) are pivotal initiators of immune responses upon activation by danger signals coming from pathogens or distressed tissues through triggering of the Toll-like receptors (TLRs). We generated in vitro murine cDCs in the absence of estrogens and measured the effects of exogenously added estrogen or BPA on their differentiation and activation by the TLR ligands LPS and CpG. Estrogen enhanced the differentiation of GM-CSF-dependent cDCs from bone marrow precursors in vitro, and the selective estrogen receptor modulators (SERMs) tamoxifen and fulvestrant blocked these effects. Moreover, estrogen augmented the upregulation of costimulatory molecules and proinflammatory cytokines (IL-12p70 and TNFα) upon stimulation by TLR9 ligand CpG, while the response to LPS was less estrogen-dependent. These effects are partially explained by an estrogen-dependent regulation of TLR9 expression. BPA did not promote cDC differentiation nor activation upon TLR stimulation. Our results suggest that estrogen promotes immune responses by increasing DC activation, with a preferential effect on TLR9 over TLR4 stimulation, and highlight the influence of estrogens in DC cultures, while BPA does not mimic estrogen in the DC functions that we tested.
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spelling pubmed-55477092017-08-15 Bisphenol A Does Not Mimic Estrogen in the Promotion of the In Vitro Response of Murine Dendritic Cells to Toll-Like Receptor Ligands Chakhtoura, Marita Sriram, Uma Heayn, Michelle Wonsidler, Joshua Doyle, Christopher Dinnall, Joudy-Ann Gallucci, Stefania Roberts, Rebecca A. Mediators Inflamm Research Article Sex hormones affect immune responses and might promote autoimmunity. Endocrine disrupting chemicals such as bisphenol A (BPA) may mimic their immune effects. Conventional dendritic cells (cDCs) are pivotal initiators of immune responses upon activation by danger signals coming from pathogens or distressed tissues through triggering of the Toll-like receptors (TLRs). We generated in vitro murine cDCs in the absence of estrogens and measured the effects of exogenously added estrogen or BPA on their differentiation and activation by the TLR ligands LPS and CpG. Estrogen enhanced the differentiation of GM-CSF-dependent cDCs from bone marrow precursors in vitro, and the selective estrogen receptor modulators (SERMs) tamoxifen and fulvestrant blocked these effects. Moreover, estrogen augmented the upregulation of costimulatory molecules and proinflammatory cytokines (IL-12p70 and TNFα) upon stimulation by TLR9 ligand CpG, while the response to LPS was less estrogen-dependent. These effects are partially explained by an estrogen-dependent regulation of TLR9 expression. BPA did not promote cDC differentiation nor activation upon TLR stimulation. Our results suggest that estrogen promotes immune responses by increasing DC activation, with a preferential effect on TLR9 over TLR4 stimulation, and highlight the influence of estrogens in DC cultures, while BPA does not mimic estrogen in the DC functions that we tested. Hindawi 2017 2017-07-25 /pmc/articles/PMC5547709/ /pubmed/28811679 http://dx.doi.org/10.1155/2017/2034348 Text en Copyright © 2017 Marita Chakhtoura et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chakhtoura, Marita
Sriram, Uma
Heayn, Michelle
Wonsidler, Joshua
Doyle, Christopher
Dinnall, Joudy-Ann
Gallucci, Stefania
Roberts, Rebecca A.
Bisphenol A Does Not Mimic Estrogen in the Promotion of the In Vitro Response of Murine Dendritic Cells to Toll-Like Receptor Ligands
title Bisphenol A Does Not Mimic Estrogen in the Promotion of the In Vitro Response of Murine Dendritic Cells to Toll-Like Receptor Ligands
title_full Bisphenol A Does Not Mimic Estrogen in the Promotion of the In Vitro Response of Murine Dendritic Cells to Toll-Like Receptor Ligands
title_fullStr Bisphenol A Does Not Mimic Estrogen in the Promotion of the In Vitro Response of Murine Dendritic Cells to Toll-Like Receptor Ligands
title_full_unstemmed Bisphenol A Does Not Mimic Estrogen in the Promotion of the In Vitro Response of Murine Dendritic Cells to Toll-Like Receptor Ligands
title_short Bisphenol A Does Not Mimic Estrogen in the Promotion of the In Vitro Response of Murine Dendritic Cells to Toll-Like Receptor Ligands
title_sort bisphenol a does not mimic estrogen in the promotion of the in vitro response of murine dendritic cells to toll-like receptor ligands
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547709/
https://www.ncbi.nlm.nih.gov/pubmed/28811679
http://dx.doi.org/10.1155/2017/2034348
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