Ratajczak-Wrona W, Nowak K, Garley M, Tynecka M, Jablonska E
Department of Immunology, Medical University of Bialystok, Białystok, Poland.
Hum Exp Toxicol. 2019 Feb;38(2):239-246. doi: 10.1177/0960327118793188. Epub 2018 Aug 16.
The aim of the study was to evaluate the effect of bisphenol A (BPA) on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by neutrophils with regard to sex and nuclear factor-κB (NF-κB) pathway participation in this process. This study demonstrated that BPA intensifies the production of NO and the expression of iNOS in the cytoplasmic fraction of neutrophils of women as well as men. In addition, an enhanced expression of NF-κB in the cytoplasmic and nuclear fraction of neutrophils exposed to BPA was observed in the cells of both sexes. The lipopolysaccharide (LPS) stimulation of neutrophils of both sexes led to an intensification of NO production and expression of all tested proteins. However, simultaneous stimulation of neutrophils of both men and women with LPS and BPA decreased the production of NO and expression of iNOS and NF-κB in both fractions compared to the cells exposed only to xenoestrogen. Moreover, expression of iNOS and NF-κB was higher in female neutrophils than in male cells. This study demonstrated that BPA affects the production of NO with the participation of iNOS by human polymorphonuclear neutrophils. This process is associated with the activation of the NF-κB pathway. In addition, different activity of NF-κB in neutrophils, observed with respect to sex, indicates a different role of this pathway in female and male cells.
本研究的目的是评估双酚A（BPA）对中性粒细胞一氧化氮（NO）生成和诱导型一氧化氮合酶（iNOS）表达的影响，并探讨性别因素以及核因子-κB（NF-κB）信号通路在这一过程中的作用。本研究表明，BPA可增强女性和男性中性粒细胞胞质部分中NO的生成及iNOS的表达。此外，在暴露于BPA的两性中性粒细胞的胞质和细胞核部分中均观察到NF-κB表达增强。脂多糖（LPS）刺激两性中性粒细胞均导致NO生成及所有检测蛋白表达增强。然而，与仅暴露于异雌激素的细胞相比，同时用LPS和BPA刺激男性和女性中性粒细胞会使两部分细胞中NO的生成以及iNOS和NF-κB的表达均降低。此外，女性中性粒细胞中iNOS和NF-κB的表达高于男性细胞。本研究表明，BPA通过人多形核中性粒细胞参与iNOS的作用来影响NO的生成。这一过程与NF-κB信号通路的激活有关。此外，观察到中性粒细胞中NF-κB的活性因性别而异，表明该信号通路在女性和男性细胞中发挥不同作用。
