Journal
TOXICOLOGY
Volume 424, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2019.06.001
Keywords
T-2 toxin; Mycotoxin; Mucin; Endoplasmic reticulum stress; E. coli O157:H7
Categories
Funding
- National Natural Science Foundation of China [31672611]
- Natural Science Foundation of Guangdong Province [2015A030312005]
- Department of Education of Guangdong Province [2018KZDXM015, 2018KTSCX021]
- Guangzhou Municipal Science and Technology Project [201804020067]
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T-2 toxin is a trichothecene mycotoxin that widely contaminates food and has a variety of toxic effects. However, the underlying mechanism of T-2 toxin on intestinal mucin remains unclear. In present study, human intestinal Caco-2 cells and HT-29 cells were treated with 100 ng/mL T-2 toxin at one-quarter of the IC50 for 24 h, which caused the inhibition of MUC2 and adhesion of E. coli O157:H7. We found T-2 toxin induced endoplasmic reticulum stress and activated the IRE1/XBP1 pathway, which may be related to the inhibition of MUC2. Interestingly, T-2 toxin activated IRE1 alpha to inhibit IRE1 beta, which optimized mucin production. Furthermore, overexpression of IRE1 beta in the cells apparently alleviated the inhibition of MUC2 caused by T-2 toxin. IRE1 alpha knock-down blocked the down-regulation of IRE1 beta and MUC2 induced by T-2 toxin. We revealed the critical role of IRE1 alpha in the inhibition of intestinal mucin. This finding was confirmed in BALB/c mice which were exposed to T-2 toxin (0.5 mg/kg bw) for 4 weeks. T-2 toxin activated the IRE1/XBP1 pathway to disrupt intestinal mucin, which lead to the imbalance of gut microbiota and an increased risk of host infection by E. coli O157:H7. T-2 toxin exposure also increased the expressions of pro-inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha in mice, which might respond to IRE1 alpha activation. Importantly, IRE1 alpha activation was a therapeutic target for intestinal inflammation caused by T-2 toxin. This study provided a new perspective to understand the intestinal toxicity of T-2 toxin.
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