College of Life Science and Engineering , Foshan University , Foshan , Guangdong 528231 , People's Republic of China.
College of Veterinary Medicine , Jilin University , Changchun , Jilin 130062 , People's Republic of China.
J Agric Food Chem. 2019 Apr 24;67(16):4588-4594. doi: 10.1021/acs.jafc.8b05948. Epub 2019 Apr 12.
Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin synthesized in Fusarium species, mainly Fusarium graminearum and Fusarium culmorum, and it has strong estrogenic activity and causes genotoxic effects, reproductive disorders, and immunosuppressive effects. Neutrophil extracellular trap (NET) has been studied for many years. Initially, NET was considered a form of the innate response that combats invading microorganisms. However, NET is involved in a series of pathophysiological mechanisms, including thrombosis, tissue necrosis, autoinflammation, and even autoimmunity. We recently found that polymorphonuclear neutrophils response to ZEA exposure by undergoing NET formation. However, the molecular mechanisms involved in this process remain poorly characterized. Here, we analyze whether estrogen receptors (ERs) can affect NET formation after ZEA stimulation. The involvement of ERs is investigated with the selective ER antagonists. Moreover, we investigate the mechanisms of NET formation using immunofluorescence staining, fluorescence microplate, and western blot analysis. Our results show that ERs (ERα and ERβ) are not involved in ZEA-induced NET formation, but reactive oxygen species (ROS), extracellular signal-regulated kinase (ERK), and p38 are postulated to be involved. Specifically, we provide data demonstrating that ZEA-induced ROS may promote activation of ERK and p38 as well as subsequent NET release. We are the first to demonstrate this new mechanism of ZEA-induced NET formation, which may help in understanding the role of ZEA in overexposure diseases and provide a relevant basis for therapeutic applications.
玉米赤霉烯酮（ZEA）是一种非甾体类雌激素真菌毒素，由镰刀菌属（主要是禾谷镰刀菌和黄色镰刀菌）合成，具有很强的雌激素活性，并导致遗传毒性、生殖障碍和免疫抑制作用。中性粒细胞胞外诱捕网（NET）已经研究了很多年。最初，NET 被认为是一种固有反应的形式，可以对抗入侵的微生物。然而，NET 参与了一系列病理生理机制，包括血栓形成、组织坏死、自身炎症，甚至自身免疫。我们最近发现，多形核粒细胞在暴露于 ZEA 时通过形成 NET 来做出反应。然而，这一过程中涉及的分子机制仍知之甚少。在这里，我们分析雌激素受体（ERs）是否可以影响 ZEA 刺激后 NET 的形成。通过使用选择性 ER 拮抗剂来研究 ERs 的参与情况。此外，我们还通过免疫荧光染色、荧光微孔板和 Western blot 分析来研究 NET 形成的机制。我们的结果表明，ERs（ERα 和 ERβ）不参与 ZEA 诱导的 NET 形成，但推测活性氧（ROS）、细胞外信号调节激酶（ERK）和 p38 参与其中。具体来说，我们提供的数据表明，ZEA 诱导的 ROS 可能促进 ERK 和 p38 的激活以及随后的 NET 释放。我们是第一个证明 ZEA 诱导的 NET 形成的这种新机制的人，这可能有助于理解 ZEA 在过度暴露疾病中的作用，并为治疗应用提供相关依据。
