Sex-dependent dysregulation of human neutrophil responses by bisphenol A.

Wioletta Ratajczak-Wrona, Marzena Garley, Malgorzata Rusak, Karolina Nowak, Jan Czerniecki, Katarzyna Wolosewicz, Milena Dabrowska, Slawomir Wolczynski, Piotr Radziwon, Ewa Jablonska
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引用次数: 11

Abstract

Background: In the present study, we aimed to investigate selected functions of human neutrophils exposed to bisphenol A (BPA) under in vitro conditions. As BPA is classified among xenoestrogens, we compared its action and effects with those of 17β-estradiol (E2).

Methods: Chemotaxis of neutrophils was examined using the Boyden chamber. Their phagocytosis and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity were assessed via Park's method with latex beads and Park's test with nitroblue tetrazolium. To assess the total concentration of nitric oxide (NO), the Griess reaction was utilized. Flow cytometry was used to assess the expression of cluster of differentiation (CD) antigens. The formation of neutrophil extracellular traps (NETs) was analyzed using a microscope (IN Cell Analyzer 2200 system). Expression of the investigated proteins was determined using Western blot.

Results: The analysis of results obtained for both sexes demonstrated that after exposure to BPA, the chemotactic capacity of neutrophils was reduced. In the presence of BPA, the phagocytic activity was found to be elevated in the cells obtained from women and reduced in the cells from men. Following exposure to BPA, the percentage of neutrophils with CD14 and CD284 (TLR4) expression, as well as the percentage of cells forming NETs, was increased in the cells from both sexes. The stimulatory role of BPA and E2 in the activation of NADPH oxidase was observed only in female cells. On the other hand, no influence of E2 on the expression of CD14 and CD284, chemotaxis, phagocytosis, and the amount of NET-positive neutrophils was found for both sexes. The study further showed that BPA intensified NO production and iNOS expression in the cells of both sexes. In addition, intensified expression of all tested PI3K-Akt pathway proteins was observed in male neutrophils.

Conclusions: The study demonstrated the influence of BPA on neutrophil functions associated with locomotion and pathogen elimination, which in turn may disturb the immune response of these cells in both women and men. Analysis of the obtained data showed that the effect of this xenoestrogen on the human neutrophils was more pronounced than E2.

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双酚A对中性粒细胞反应的性别依赖性失调。
背景:在本研究中,我们旨在研究体外条件下暴露于双酚A (BPA)的人中性粒细胞的选择功能。由于BPA被归类为异种雌激素,我们将其与17β-雌二醇(E2)的作用和作用进行了比较。方法:采用博伊登室法检测中性粒细胞趋化性。用Park的乳胶珠法和Park的硝基蓝四氮唑法测定了它们的吞噬能力和烟酰胺腺嘌呤二核苷酸磷酸氢氧化酶(NADPH)氧化酶活性。采用Griess反应测定一氧化氮(NO)总浓度。采用流式细胞术检测细胞中CD抗原的表达情况。使用显微镜(IN Cell Analyzer 2200系统)分析中性粒细胞胞外陷阱(NETs)的形成。Western blot检测所研究蛋白的表达。结果:两性结果分析表明,暴露于双酚a后,中性粒细胞的趋化能力降低。在BPA存在的情况下,从女性身上获得的细胞的吞噬活性升高,而从男性身上获得的细胞的吞噬活性降低。暴露于BPA后,两性细胞中表达CD14和CD284 (TLR4)的中性粒细胞百分比以及形成NETs的细胞百分比均有所增加。双酚a和E2对NADPH氧化酶激活的刺激作用仅在雌性细胞中观察到。另一方面,E2对两性小鼠CD14和CD284的表达、趋化性、吞噬作用和net阳性中性粒细胞的数量均无影响。研究进一步表明,双酚a增强了两性细胞中NO的产生和iNOS的表达。此外,所有检测的PI3K-Akt通路蛋白在男性中性粒细胞中表达增强。结论:该研究表明BPA对中性粒细胞运动和病原体消除相关功能的影响,进而可能干扰这些细胞的免疫反应。对所得数据的分析表明,该异种雌激素对人中性粒细胞的影响比E2更明显。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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