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Mediators of Inflammation
Volume 2017 (2017), Article ID 2034348, 12 pages
Research Article

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

1Laboratory of Dendritic Cell Biology, Department of Microbiology-Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
2Division of Rheumatology, Joseph Jr. Stokes Research Institute, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
3Department of Biology, Ursinus College, Collegeville, PA 19426, USA
4Biochemistry and Molecular Biology Program, Ursinus College, Collegeville, PA 19426, USA

Correspondence should be addressed to Stefania Gallucci; ude.elpmet@iccullag

Received 29 November 2016; Revised 25 April 2017; Accepted 5 June 2017; Published 25 July 2017

Academic Editor: Alex Kleinjan

Copyright © 2017 Marita Chakhtoura et al. 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.


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.