Interruption of immune responses in primary macrophages exposed to nonylphenol provides insights into the role of ER and NF-KB in immunotoxicity of Persian sturgeon

Abstract

The severe decline in population of sturgeons due to pollution highlighted poor understanding about the immunotoxicological responses of sturgeons. This study was designed in three experiments to find out how nonylphenol (NP) interrupts some pro-inflammatory immune parameters in macrophages from Persian sturgeon (Acipencer persicous) as the oldest vertebrate model conserving intact innate immune system. After determination of IC50 values of NP (200 μM), some pro-inflammatory immune parameters and induced apoptosis in macrophages at low dose (10 nM) and high dose (100 nM) of NP and of 17β estradiol (E2) (positive control) were determined after 6, 24 and 48 h of the exposure (as the first experiment). The two doses of NP induced pro-inflammatory reaction and apoptosis with strong correlations, whereas this result was observed more obviously in high dose of E2. In the second experiments, the macrophages were exposed to the two doses of NP along with estrogen receptor alpha (ERα) antagonist, which consequently decreased the induction of pro-inflammatory reactions. Similarly, in the third experiment, NF-KB and ERα antagonists were used and pro-inflammatory reactions decreased compared to the control group (P < 0.05). Decreasing correlation between immune parameters following the second and third experiments verified interaction between ERα and NF-KB pathways. Thus, NP could be immune disrupter and apoptosis inducer in sturgeon macrophages in vitro, even in low dose. For the first time, this study revealed that NP can induce pro-inflammatory reactions in macrophages derived from sturgeons.