In vitro impact of bisphenols BPA, BPF, BPAF and 17β-estradiol (E2) on human monocyte-derived dendritic cell generation, maturation and function

Bisphenols (BPs) are widely spread pollutants that act as estrogen-like endocrine disruptors and are potentially affecting human health on a long run. We explored the effects of BPA, BPF and BPAF, on in vitro differentiation and maturation of MDDCs. Monocytes were treated with 17 beta-estradiol (E2) and each BP at the beginning of their differentiation into iMDDC5. We found that 10 and 50 mu M of BPA and BPF, 10 and 30 mu M of BPAF and 10 and 50 nM of E2 did not affect cell viability. However, 50 mu M of BPA and BPF, as well as 10 and 30 mu M of BPAF, significantly decreased the endocytotic capacity of iMDDCs. Both, BPA (50 mu M) and BPAF (30 mu M) decreased the expression of CD1a and increased the amount of DC-SIGN molecules on iMDDCs. The E2 pre-treatment moderately decreased expression of CD80, CD86 and CD83 co-stimulatory molecules while increasing the numbers of HLA-DR on mMDDCs. Only BPAF significantly influenced the expression of CD80 and CD86 (both decreased), as well as CD83 and HLA-DR molecules (both increased) on mMDDCs. In addition, BPAF modulated DC maturation signaling pathways by lowering the phosphorylation of p65 NF-kappa B (nuclear factor-kappaB) and ERK (extracellular signal regulated kinase) 1/2 proteins. Consequently, the in vitro proliferation of allogeneic T cells, stimulated with differently pre-treated iMDDC5 and mMDDCs, was significantly reduced only in case of BPAF. (C) 2016 Elsevier B.V. All rights reserved.