27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression: A key target potentially linking zearalenone and cancer

被引：3

作者：

Ruan, Haonan ^{[1
]}

Zhang, Jing ^{[1
]}

Wang, Yunyun ^{[1
]}

Huang, Ying ^{[1
]}

Wu, Jiashuo ^{[1
]}

He, Chunjiao ^{[1
]}

Ke, Tongwei ^{[1
]}

Luo, Jiaoyang ^{[1
]}

Yang, Meihua ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev, Key Lab Bioact Subst & Resources Utilizat Chinese, Minist Educ, Beijing 100193, Peoples R China

来源：

JOURNAL OF PHARMACEUTICAL ANALYSIS | 2024年 / 14卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Zearalenone; Intestinal immunosuppression; Apolipoprotein E; Bioinformatics analysis; Cancer; ALZHEIMERS-DISEASE; ACTIVATION; CELLS; MYCOTOXINS; EXPRESSION; INNATE; MICE;

D O I：

10.1016/j.jpha.2023.08.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Zearalenone (ZEN) is a mycotoxin that extensively contaminates food and feed, posing a significant threat to public health. However, the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear. In this study, Sprague-Dawley (SD) rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w. for a duration of 14 days. The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine. Furthermore, ZEN exposure caused a significant reduction in the levels of apolipoprotein E (ApoE) and liver X receptor (LXR) (P < 0.05). Conversely, it upregulated the levels of myeloidderived suppressor cells (MDSCs) markers (P < 0.05) and decreased the presence of 27-hydroxycholesterol (27-HC) in the intestine (P < 0.05). It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN. Additionally, a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal, breast, and lung cancers. These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine. Notably, ApoE may emerge as a pivotal target linking ZEN exposure to cancer development. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：371 / 388

页数：18