Macrophage MAPK7/AhR/STAT3 Signaling Mediates Mitochondrial ROS Burst and Enterohepatic Inflammatory Responses Induced by Deoxynivalenol Relevant to Low-Dose Exposure in Children

• DOI: 10.1021/acs.est.4c05875
• Publication Date: 2024-10-08T08:29:12Z
• Authors: Qi Zhang; Ming Liu; Jing Zhang; Huiyu Jiang; Chuanmin Ma; Yuanzhi Jian; Yongchang Chen; Hui Liu; Hanri Chen; Jiaqi Chen; Xiulan Sun; Jia-Sheng Wang; Xiulan Zhao; Xingyi Geng; Fuyong Song; Jun Zhou
• Keywords: Mitochondrial ROS

Deoxynivalenol (DON) can induce endoplasmic reticulum (ER) stress, mitochondrial ROS burst, and macrophage polarization. Here, we investigated the mechanism linking above three aspects with dose range relevant to low-level exposure in children. At 0.5 μg/kg bw/day, found remarkable liver gut inflammatory responses after 6-week mice age comparable humans 7-12 years old. Through antioxidant intervention, that played a driver role polarization induced by DON gut. Further bioinformatics analysis uncovered ER stress-associated protein MAPK7 (ERK5) may bind AhR initiate burst M1 The downstream cellular events of MAPK7-AhR interaction be mediated AhR/STAT3/p-STAT(Ser727) pathway. This was further supported toxicity mitigation using cyanidin-3-glucoside (C-3-G), which docks oligomerization region 200-400 aa disrupts interaction. Overall, our study provides novel evidence for DON-induced system. Our findings call attention health risks associated prepuberty children population.