Deoxynivalenol enhances IL-1ß expression in BV2 microglial cells through activation of the NF-κB pathway and the ASC/NLRP3 inflammasome

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Ilandarage Menu Neelaka Molagoda
Seunghun Lee
Rajapaksha Gedara Prasad Tharanga Jayasooriya
Cheng-Yung Jin
Yung Hyun Choi
Gi-Young Kim

Abstract

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-1β expression through the activation of the nuclear factor-κB (NF-κB) 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-1β expression from between 0.5 h and 6 h after treatment, and enhanced the nuclear localization of the NF-κB subunits, p50 and p65. NF-κB inhibitors, pyrrolidinedithiocarbamate and PS1145, significantly suppressed the DON-induced IL-1β expression, which indicated that DON increased IL-1β expression through the activation of NF-κB. In addition, marked secretion of IL-1β protein occurred in the presence of DON at 24 h, and a caspase-1 inhibitor suppressed DON-mediated IL-1β secretion, which suggested that caspase-1 induced the cleavage of pro-IL-1β 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-1β secretion, but not IL-1β gene expression, which indicated that DON promoted IL-1β secretion through the ASC/NLRP3 inflammasome. Collectively, the data suggested that DON induced IL-1β expression in BV2 microglial cells through the activation of the NF-κB signaling pathway and the subsequent upregulation of the ASC/NLRP3 inflammasome. Therefore, DON may induce inflammatory diseases or disorders by activating IL-1β expression.

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How to Cite
Molagoda, I. M. N., Lee, S., Jayasooriya, R. G. P. T., Jin, C.-Y., Choi, Y. H., & Kim, G.-Y. (2019). Deoxynivalenol enhances IL-1ß expression in BV2 microglial cells through activation of the NF-κB pathway and the ASC/NLRP3 inflammasome. EXCLI Journal, 18, 356-369. https://doi.org/10.17179/excli2018-1974
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Original articles