Nowak Karolina, Jabłońska Ewa, Ratajczak-Wrona Wioletta
Department of Immunology, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland.
Cells. 2021 Jul 16;10(7):1799. doi: 10.3390/cells10071799.
The proper functioning of the immune system is critical for an effective defense against pathogenic factors such as bacteria and viruses. All the cellular processes taking place in an organism are strictly regulated by an intracellular network of signaling pathways. In the case of immune cells, the NF-κB pathway is considered the key signaling pathway as it regulates the expression of more than 200 genes. The transcription factor NF-κB is sensitive to exogenous factors, such as xenoestrogens (XEs), which are compounds mimicking the action of endogenous estrogens and are widely distributed in the environment. Moreover, XE-induced modulation of signaling pathways may be crucial for the proper development of the immune system. In this review, we summarize the effects of XEs on the NF-κB signaling pathway. Based on our analysis, we constructed a model of XE-induced signaling in immune cells and found that in most cases XEs activate NF-κB. Our analysis indicated that the indirect impact of XEs on NF-κB in immune cells is related to the modulation of estrogen signaling and other pathways such as MAPK and JAK/STAT. We also summarize the role of these aspects of signaling in the development and further functioning of the immune system in this paper.
免疫系统的正常运作对于有效抵御细菌和病毒等致病因素至关重要。生物体中发生的所有细胞过程都受到细胞内信号通路网络的严格调控。就免疫细胞而言,NF-κB通路被认为是关键的信号通路,因为它调控着200多个基因的表达。转录因子NF-κB对外源因素敏感,如异雌激素(XEs),这些化合物模拟内源性雌激素的作用,广泛分布于环境中。此外,XEs诱导的信号通路调节可能对免疫系统的正常发育至关重要。在本综述中,我们总结了XEs对NF-κB信号通路的影响。基于我们的分析,我们构建了免疫细胞中XEs诱导信号的模型,发现大多数情况下XEs会激活NF-κB。我们的分析表明,XEs对免疫细胞中NF-κB的间接影响与雌激素信号通路以及其他通路如MAPK和JAK/STAT的调节有关。我们还在本文中总结了这些信号通路方面在免疫系统发育和进一步运作中的作用。