27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression:A key target potentially linking zearalenone and cancer
10.1016/j.jpha.2023.08.002
- Author:
Ruan HAONAN
1
;
Zhang JING
;
Wang YUNYUN
;
Huang YING
;
Wu JIASHUO
;
He CHUNJIAO
;
Ke TONGWEI
;
Luo JIAOYANG
;
Yang MEIHUA
Author Information
1. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine,Ministry of Education,Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing,100193,China
- Keywords:
Zearalenone;
Intestinal immunosuppression;
Apolipoprotein E;
Bioinformatics analysis;
Cancer
- From:
Journal of Pharmaceutical Analysis
2024;14(3):371-388
- CountryChina
- Language:Chinese
-
Abstract:
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 immunosup-pression 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 find-ings 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.
