Selenium maintains intestinal epithelial cells to activate M2 macrophages against deoxynivalenol injury

文献类型： 外文期刊

第一作者： Fan, Shijie

作者： Fan, Shijie;Chen, Jiaying;Tian, Huihui;Yang, Xinting;Zhou, Longzhu;Zhao, Qingyu;Qin, Yuchang;Zhang, Junmin;Tang, Chaohua;Tang, Chaohua

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关键词： Selenium; GPX4; Deoxynivalenol; Ferroptosis; Intestinal epithelial cells; CSF-1-M2 macrophages axis

期刊名称：FREE RADICAL BIOLOGY AND MEDICINE （ 影响因子：7.4； 五年影响因子：7.9 ）

ISSN： 0891-5849

年卷期： 2024 年 219 卷

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收录情况： SCI

摘要： Selenium (Se) is indispensable in alleviating various types of intestinal injuries. Here, we thoroughly investigated the protective effect of Se on the regulation of the epithelial cell-M2 macrophages pathway in deoxynivalenol (DON)-induced intestinal damage. In the present study, Se has positive impacts on gut health by improving gut barrier function and reducing the levels of serum DON in vivo. Furthermore, our study revealed that Se supplementation increased the abundances of GPX4, p-PI3K, and AKT, decreased the levels of 4-HNE and inhibited ferroptosis. Moreover, when mice were treated with DON and Fer-1(ferroptosis inhibitor), ferroptosis was suppressed and PI3K/AKT pathway was activated. These results indicated that GPX4-PI3K/AKT-ferroptosis was a predominant pathway in DON-induced intestinal inflammation. Interestingly, we discovered that both the number of M2 anti-inflammatory macrophages and the levels of CSF-1 decreased while the pro-inflammatory cytokine IL-6 increased in the intestine and MODE-K cells supernatant. Therefore, Se supplementation activated the CSF-1-M2 macrophages axis, resulting in a decrease in IL-6 expression and an enhancement of the intestinal anti-inflammatory capacity. This study provides novel insights into how intestinal epithelial cells regulate the CSF-1-M2 macrophage pathway, which is essential in maintaining intestinal homeostasis confer to environmental hazardous stimuli.

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