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

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

SUBMITTER: Molagoda IMN

PROVIDER: S-EPMC6635726 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Molagoda Ilandarage Menu Neelaka IMN Lee Seunghun S Jayasooriya Rajapaksha Gedara Prasad Tharanga RGPT Jin Cheng-Yung CY Choi Yung Hyun YH Kim Gi-Young GY

EXCLI journal 20190611

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-G<sub>1</sub> cells was observed. DON also upregulated <i>IL-1β< ...[more]

PMID: 31338007

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Dataset Information

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

Publications

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

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