Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor alpha/beta(ER alpha/beta)-dependent mechanism with the evidence of ER alpha/beta antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor kappa B (NF-kappa B) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health. (C) 2014 Elsevier Inc. All rights reserved.