The In Vitro Immune Modulatory Effect of Bisphenol A on Fish Macrophages via Estrogen Receptor α and Nuclear Factor-κB Signaling

Bisphenol A (BPA) is a well-known environmental endocrine-disrupting chemical. Employing primary macrophages from head kidney of red common carp (<i>Cyprinus carpio</i>), the present study aimed to evaluate the immune modulatory effect of BPA and to explore its potential action mechanism associated with estrogen receptor (ER) and nuclear factor-κB (NF-κB) pathways. A dynamic response process was observed in macrophages upon various concentrations of BPA exposure, which significantly enhanced the antibacterial activity of macrophages at 0.1, 1, or 10 μg/L, but instead induced the apoptosis at 100, 1000, and 10 000 μg/L. A potential pro-inflammatory effect of BPA exposure was suggested, judging from the increased production of nitrite oxide and reactive oxygen species (ROS), the induction of <i>interleukin-1β</i> mRNA and protein, as well as <i>NF-κB</i> and other <i>NF-κB-</i>associated immune gene expression. Following BPA coexposure with the ER or NF-κB antagonist, the induction of ROS, <i>ERα</i>, and <i>NF-κB-</i>associated immune gene expression was significantly inhibited, implying interaction between those two pathways. This study thus indicated that low doses of BPA exposure alone could significantly disturb the immune response of fish primary macrophages in vitro, and for the first time revealed the synergistic action of ERα and NF-κB transcription factors in the BPA effect