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7180584 
Journal Article 
DEOXYNIVALENOL ENHANCES IL-1 beta EXPRESSION IN BV2 MICROGLIAL CELLS THROUGH ACTIVATION OF THE NF-KB PATHWAY AND THE ASC/NLRP3 INFLAMMASOME 
Molagoda, IMN; Lee, S; Jayasooriya, R; Jin, CY; Choi, YH; Kim, GiY; , 
2019 
Yes 
EXCLI Journal
ISSN: 1611-2156 
EXCLI JOURNAL MANAGING OFFICE 
DORTMUND 
18 
356-369 
English 
31338007 
WOS:000472797400001 
Deoxynivalenol (DON) is one of the most common fungal toxins that contaminate food grains and cereal-derived products. However, it is unknown whether DON stimulates IL-1 beta expression through the activation of the nuclear factor-kappa B (NF kappa KB) pathway and the ACS/NLRP3 inflammasome. In this study, we found that high concentrations of DON (above 800 nM) decreased relative cell viability; however, no significant population of apoptotic sub-G1 cells was observed. DON also upregulated IL-1 beta expression from between 0.5 h and 6 h after treatment, and enhanced the nuclear localization of the NF-kappa B subunits, p50 and p65. NF-kappa B inhibitors, pyrrolidinedithiocarbamate and PS1145, significantly suppressed the DON-induced IL-1 beta expression, which indicated that DON increased IL-1 beta expression through the activation of NF-kappa B. In addition, marked secretion of IL-1 beta protein occurred in the presence of DON at 24 h, and a caspase-1 inhibitor suppressed DON-mediated IL-1 beta secretion, which suggested that caspase-1 induced the cleavage of pro-IL-1 beta to lead the secretion of its active form. Thus, components of the inflammasome, such as ASC and NLRP3, significantly increased by DON treatment; in addition, the knockdown of ASC and NLRP3 markedly downregulated DON-induced IL-1 beta secretion, but not IL-1 beta gene expression, which indicated that DON promoted IL-1 beta secretion through the ASC/NLRP3 inflammasome. Collectively, the data suggested that DON induced IL-1 beta expression in BV2 microglial cells through the activation of the NF-kappa B signaling pathway and the subsequent upregulation of the ASC/NLRP3 inflammasome. Therefore, DON may induce inflammatory diseases or disorders by activating IL-1 beta expression.