Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Kraków, Kraków, Poland.
Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Kraków, Kraków, Poland.
Reprod Toxicol. 2019 Jun;86:14-22. doi: 10.1016/j.reprotox.2019.03.003. Epub 2019 Mar 20.
We determined the action of a mixture of 16 priority PAHs present in high concentrations in maternal blood (Mix I) and the same but in low concentrations detected in placental tissue (Mix II) on AhR, ERα, NFκB, CYP1A1, CYP1B1, and COMT protein expression and cell proliferation of JEG-3 and BeWo cell lines. Both mixtures induced AhR expression in JEG-3 and BeWo; however, in JEG-3 cells expression of ERα, CYP1A1, CYP1B1, and COMT was upregulated, while in BeWo cells downregulated. The opposite effect of mixtures on NFκB protein expression (inhibitory in JEG-3, stimulatory in BeWo) was noted. We suggest AhR-mediated activation of PAHs metabolism in JEG-3 cells, and AhR interaction with NFκB and AhR cross-talk with ERα causing inhibition of detoxification in BeWo cells. As a result there was a stimulatory effect on JEG-3 and an inhibitory one on BeWo cell proliferation.
我们测定了高浓度母体血液中(混合物 I)和低浓度胎盘组织中(混合物 II)同时存在的 16 种优先多环芳烃混合物对 AhR、ERα、NFκB、CYP1A1、CYP1B1 和 COMT 蛋白表达以及 JEG-3 和 BeWo 细胞系细胞增殖的作用。两种混合物均诱导 JEG-3 和 BeWo 中 AhR 的表达;然而,在 JEG-3 细胞中,ERα、CYP1A1、CYP1B1 和 COMT 的表达上调,而在 BeWo 细胞中则下调。还注意到混合物对 NFκB 蛋白表达的相反作用(在 JEG-3 中抑制,在 BeWo 中刺激)。我们认为,多环芳烃在 JEG-3 细胞中的代谢通过 AhR 介导激活,而 AhR 与 NFκB 的相互作用以及 AhR 与 ERα 的交叉对话导致 BeWo 细胞解毒作用受到抑制。结果,JEG-3 细胞增殖受到刺激,而 BeWo 细胞增殖受到抑制。