肝X受体
玉米赤霉烯酮
下调和上调
载脂蛋白E
免疫抑制
受体
真菌毒素
癌症研究
细胞凋亡
生物
内科学
内分泌学
核受体
免疫学
医学
生物化学
植物
疾病
转录因子
基因
作者
Haonan Ruan,Jing Zhang,Yunyun Wang,Ying Huang,Jiashuo Wu,Chunjiao He,Tongwei Ke,Jiaoyang Luo,Meihua Yang
标识
DOI:10.1016/j.jpha.2023.08.002
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 myeloid-derived 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.
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