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.
Highlights
A growing body of scientific research has suggested that environmental pollutants, including endocrine disruptor chemicals (EDCs), could interfere on human health, leading to hormonal, immune and metabolic perturbations [1,2,3]
BPA stimulates the proliferation of peripheral blood mononuclear cells (PBMCs)
In order to address the possible effects of BPA (0.1nM and 1nM) on PBMCs proliferation, we performed experiments on cells from 12 adult healthy donors, by brief exposure either at steady state condition or under polyclonal mitogens, as PHA and anti-CD3/CD28 stimuli (Fig 1)
Summary
A growing body of scientific research has suggested that environmental pollutants, including endocrine disruptor chemicals (EDCs), could interfere on human health, leading to hormonal, immune and metabolic perturbations [1,2,3]. The mechanisms by which BPA exerts all these biological actions are still not fully understood and, the large body of studies have been done in animal models, being very few data available in human immune systems [27] In this context, considering the controversial reports on the implications of BPA in human health, aim of this study was to check the effects of a short time exposure to very low concentration of BPA on proliferation, differentiation and function of immune cells. Considering the controversial reports on the implications of BPA in human health, aim of this study was to check the effects of a short time exposure to very low concentration of BPA on proliferation, differentiation and function of immune cells To address these aspects, we used freshly isolated peripheral blood mononuclear cells (PBMCs) and monocytes-derived dendritic cells (mDCs) from adult healthy volunteers, at basal condition and after mitogen activation
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