Abstract
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.
Highlights
In 1986, in the journal Cell, Sen and Baltimore described for the first time the transcription factor NF-κB, which is a central element of the signaling pathway and is considered the main regulator that controls the expression of inflammatory mediators in immune cells [1]
We have considered the relationship between NF-κB and estrogen signaling in immune cells exposed to XEs, as well as we discussed the role of the above interactions for development of embryos immune system and their further functioning
bisphenol A (BPA) suppressed LPS-induced NF-κB activation in a dose-dependent manner [109], whereas a dose-dependent increase of NF-κB-dependent luciferase gene expression was observed in RAW264.7 macrophages exposed to other XEs, namely DDT (0.2, 0.5, or 1 μM) without prior activation of cells by LPS
Summary
In 1986, in the journal Cell, Sen and Baltimore described for the first time the transcription factor NF-κB, which is a central element of the signaling pathway and is considered the main regulator that controls the expression of inflammatory mediators in immune cells [1]. Due to the latest trends promoting an ecological and healthy lifestyle, researchers show an increasing interest in the exposure of humans to chemical substances, which are found in food, drugs, cosmetics, plastics, and detergents (Table 1) [4,5,6,7,8,9,10,11,12] Some ingredients of these products are substances that mimic the action of endogenous estrogens and are collectively known as xenoestrogens (XEs) (Figure 1) [13,14,15,16,17,18,19].
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