title: Human Peripheral Blood Mononuclear Cell Function and Dendritic Cell Differentiation Are Affected by Bisphenol-A Exposure.
abstract: Environmental pollutants, including endocrine disruptor chemicals (EDCs), interfere on human health, leading to hormonal, immune and metabolic perturbations. Bisphenol-A (BPA), a main component of polycarbonate plastics, has been receiving increased attention due to its worldwide distribution with a large exposure. In humans, BPA, for its estrogenic activity, may have a role in autoimmunity, inflammatory and allergic diseases. To this aim, we assessed the effect of low BPA doses on functionality of human peripheral blood mononuclear cells (PBMCs), and on in vitro differentiation of dendritic cells from monocytes (mDCs). Fresh peripheral blood samples were obtained from 12 healthy adult volunteers. PBMCs were left unstimulated or were activated with the mitogen phytohemagglutinin (PHA) or the anti-CD3 and anti-CD28 antibodies and incubated in presence or absence of BPA at 0.1 and 1nM concentrations. The immune-modulatory effect of BPA was assessed by evaluating the cell proliferation and the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) secreted by PBMCs. mDCs were differentiated with IL-4 and GC-CSF with or without BPA and the expression of differentiation/maturation markers (CD11c, CD1a, CD86, HLA-DR) was evaluated by flow cytometry; furthermore, a panel of 27 different cytokines, growth factors and chemokines were assayed in the mDC culture supernatants. PBMCs proliferation significantly increased upon BPA exposure compared to BPA untreated cells. In addition, a significant decrease in IL-10 secretion was observed in PBMCs incubated with BPA, either in unstimulated or mitogen-stimulated cells, and at both 0.1 and 1nM BPA concentrations. Similarly, IL-13 was reduced, mainly in cells activated by antiCD3/CD28. By contrast, no significant changes in IFN-γ and IL-4 production were found in any condition assayed. Finally, BPA at 1nM increased the density of dendritic cells expressing CD1a and concomitantly decreased the expression of HLA-DR and CD86 activation markers. In conclusion, in humans the exposure to BPA causes on PBMCs a significant modulation of proliferative capacity and cytokine production, and on mDCs alteration in differentiation and phenotype. These immune cell alterations suggest that low dose chronic exposure to BPA could be involved in immune deregulation and possibly in the increased susceptibility to develop inflammatory and autoimmune diseases.
authors: Institute of Food Science (ISA), National Council of Research (CNR), via Roma 64-83100, Avellino, Italy.
authors: Alessandra
authors: A
authors: Camarca
authors: Institute of Protein Biochemistry (IBP), CNR, via P. Castellino 11-80131, Naples, Italy.
authors: Carmen
authors: C
authors: Gianfrani
authors: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini 5-80131, Naples, Italy.
authors: Fabiana
authors: F
authors: Ariemma
authors: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini 5-80131, Naples, Italy.
authors: Ilaria
authors: I
authors: Cimmino
authors: Department of Public Health, Federico II University of Naples, via S. Pansini 5-80131, Naples, Italy.
authors: Dario
authors: D
authors: Bruzzese
authors: Institute of Food Science (ISA), National Council of Research (CNR), via Roma 64-83100, Avellino, Italy.
authors: Roberta
authors: R
authors: Scerbo
authors: Institute of Protein Biochemistry (IBP), CNR, via P. Castellino 11-80131, Naples, Italy.
authors: Stefania
authors: S
authors: Picascia
authors: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini 5-80131, Naples, Italy.|URT "Genomic of Diabetes", Institute of Experimental Endocrinology and Oncology (IEOS), CNR, via S. Pansini 5-80131, Naples, Italy.
authors: Vittoria
authors: V
authors: D'Esposito
authors: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini 5-80131, Naples, Italy.|URT "Genomic of Diabetes", Institute of Experimental Endocrinology and Oncology (IEOS), CNR, via S. Pansini 5-80131, Naples, Italy.
authors: Francesco
authors: F
authors: Beguinot
authors: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini 5-80131, Naples, Italy.|URT "Genomic of Diabetes", Institute of Experimental Endocrinology and Oncology (IEOS), CNR, via S. Pansini 5-80131, Naples, Italy.
authors: Pietro
authors: P
authors: Formisano
authors: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini 5-80131, Naples, Italy.|URT "Genomic of Diabetes", Institute of Experimental Endocrinology and Oncology (IEOS), CNR, via S. Pansini 5-80131, Naples, Italy.
authors: Rossella
authors: http://orcid.org/0000-0003-3440-8189
authors: R
authors: Valentino
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010636:Phenols / Q000633:toxicity*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D016753:Interleukin-10; D018793:Interleukin-13; D010636:Phenols; C508609:IL10 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds