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, Chris; Dinnall, Joudy-Ann; Gallucci, Stefania; Roberts, Rebecca

doi:10.1155/2017/2034348

Cited by 7 publications

(4 citation statements)

References 58 publications

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“…(2014c) [RefID 4533] at 10 nM, Zhu et al (2015) [RefID 9100], Chen et al (2018c) [RefID 11728] at 100 nM, Li et al (2018a) [RefID 12475] at 8.76 nM, Tajiki‐Nishino et al (2018) [RefID 13221] at 1 nM; modulation of histone methylation by Li et al (2018a) [RefID 12475] at 8.76 nM and modulation of ER signalling pathways, where effects were reversed by ERa/b antagonists by Couleau et al (2015) [RefID 1316] at 100 nM, Liu et al (2014c) [RefID 4533] at 10 nM, Chen et al (2018c) [RefID 11728] at 100 nM. In contrast to the latter findings, Chakhtoura et al (2017) [RefID 927] found no effects on cytokine expression and no influence on dendritic cell maturation at concentrations as low as 0.05 nM, while the positive control treatment at the same concentration with β‐E2 did.…”

Section: Assessmentmentioning

confidence: 99%

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Lambré¹,

Baviera²,

Bolognesi³

et al. 2023

EFS2

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In 2015, EFSA established a temporary tolerable daily intake (t‐TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re‐evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re‐evaluation, a pre‐established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57–73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure.

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Section: Assessmentmentioning

confidence: 99%

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Lambré¹,

Baviera²,

Bolognesi³

et al. 2023

EFS2

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“…Most common material used to mimic DC activation when provoked by bacteria is LPS, a characteristic component of the wall of Gramnegative bacteria [46,47]. However, due to its possible toxicity, LPS is only used in research protocols.…”

Section: In Vitro Maturation Of Modcsmentioning

confidence: 99%

In Laboratory Generation and Maturation of Human Monocyte-Derived Dendritic Cells for Cancer Immunotherapy

Mishra¹,

Bharadva²,

Joshi

et al. 2020

Int J App Pharm

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Dendritic cells (DCs) play a critical role in the regulation of adaptive immune responses, furthermore they act as a bridge between the innate and the adaptive immune systems they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. The first reported trial using DCs in 1995, since they have been used in trials all over the world for several of indications, including cancer and human immunodeficiency virus infection. Generally, for in vitro experiments or for DCs vaccination monocyte-derived dendritic cells (moDCs) were generated from purified monocytes that isolated from peripheral blood by density gradient centrifugation. A variety of methods can be used for enrichment of monocytes for generation of clinical-grade DCs. Herein we summarized up to date understanding of systems and inputs used in procedures to differentiate DCs from blood monocytes in vitro.

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“…Interestingly, it is not yet understood why women are at a higher risk of developing autoimmune diseases such as SLE, rheumatoid arthritis, Graves’ disease, and thyroiditis following menopause ( 45 ). EDCs are able to exert agonistic or antagonistic roles on normal physiological sex hormone actions, enhancing or mitigating hormonal effects on immune cells ( 25 , 46 – 48 ). As with many endocrine components, sex hormones and EDCs exert differential effects, not only due to dosage but also in temporally dependent and context-specific manners.…”

Section: Sex Hormones and Environmental Edc Regulation Of Immunity Anmentioning

confidence: 99%

Our Environment Shapes Us: The Importance of Environment and Sex Differences in Regulation of Autoantibody Production

2018

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Consequential differences exist between the male and female immune systems’ ability to respond to pathogens, environmental insults or self-antigens, and subsequent effects on immunoregulation. In general, females when compared with their male counterparts, respond to pathogenic stimuli and vaccines more robustly, with heightened production of antibodies, pro-inflammatory cytokines, and chemokines. While the precise reasons for sex differences in immune response to different stimuli are not yet well understood, females are more resistant to infectious diseases and much more likely to develop autoimmune diseases. Intrinsic (i.e., sex hormones, sex chromosomes, etc.) and extrinsic (microbiome composition, external triggers, and immune modulators) factors appear to impact the overall outcome of immune responses between sexes. Evidence suggests that interactions between environmental contaminants [e.g., endocrine disrupting chemicals (EDCs)] and host leukocytes affect the ability of the immune system to mount a response to exogenous and endogenous insults, and/or return to normal activity following clearance of the threat. Inherently, males and females have differential immune response to external triggers. In this review, we describe how environmental chemicals, including EDCs, may have sex differential influence on the outcome of immune responses through alterations in epigenetic status (such as modulation of microRNA expression, gene methylation, or histone modification status), direct and indirect activation of the estrogen receptors to drive hormonal effects, and differential modulation of microbial sensing and composition of host microbiota. Taken together, an intriguing question develops as to how an individual’s environment directly and indirectly contributes to an altered immune response, dysregulation of autoantibody production, and influence autoimmune disease development. Few studies exist utilizing well-controlled cohorts of both sexes to explore the sex differences in response to EDC exposure and the effects on autoimmune disease development. Translational studies incorporating multiple environmental factors in animal models of autoimmune disease are necessary to determine the interrelationships that occur between potential etiopathological factors. The presence or absence of autoantibodies is not a reliable predictor of disease. Therefore, future studies should incorporate all the susceptibility/influencing factors, coupled with individual genomics, epigenomics, and proteomics, to develop a model that better predicts, diagnoses, and treats autoimmune diseases in a personalized-medicine fashion.

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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

Cited by 7 publications

References 58 publications

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

In Laboratory Generation and Maturation of Human Monocyte-Derived Dendritic Cells for Cancer Immunotherapy

Our Environment Shapes Us: The Importance of Environment and Sex Differences in Regulation of Autoantibody Production

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