Authors: | Molagoda, Ilandarage Menu Neelaka Lee, Seunghun Jayasooriya, Rajapaksha Gedara Prasad Tharanga Jin, Cheng-Yung Choi, Yung Hyun Kim, Gi-Young |
Title: | Deoxynivalenol enhances IL-1ß expression in BV2 microglial cells through activation of the NF-κB pathway and the ASC/NLRP3 inflammasome |
Language (ISO): | en |
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 β expression through the activation of the nuclear factor- κ B (NF- κ B) pathway and the ACS/NLRP3 inflammasome. In this study, we found that high concentrations of DON (above 800 nM) decreased relative cell viability; ho wever, no significant population of apoptotic sub-G 1 cells was observed. DON also upregulated IL-1 β expression from between 0.5 h and 6 h after treatment, and enhanced the nuclear localization of the NF- κ B subunits, p50 and p65. NF- κ B inhibitors, pyrrolidinedithiocarba- mate and PS1145, significantly suppressed the DON-induced IL-1 β expression, which indicated that DON in- creased IL-1 β expression through the activation of NF- κ B. In addition, marked secretion of IL-1 β protein occurred in the presence of DON at 24 h, and a caspase-1 inhibitor suppressed DON-mediated IL-1 β secretion, which sug- gested that caspase-1 indu ced the cleavage of pro-IL-1 β 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 knock- down of ASC and NLRP3 markedly downregulated DON-induced IL-1 β secretion, but not IL-1 β gene expression, which indicated that DON promoted IL-1 β secretion through the ASC/NLRP3 inflammasome. Co llectively, the data suggested that DON induced IL-1 β expression in BV2 microglial cells through the activation of the NF- κ B signaling pathway and the subsequent upregulation of the ASC/NLRP3 inflammasome. Therefore, DON may in- duce inflammatory diseases or disorders by activating IL-1 β expression. |
Subject Headings: | Deoxynivalenol IL-1 β Nuclear factor- κ B Inflammasome |
URI: | http://hdl.handle.net/2003/38561 http://dx.doi.org/10.17877/DE290R-20480 |
Issue Date: | 2019-06-11 |
Rights link: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | Original Articles |
Files in This Item:
File | Description | Size | Format | |
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Kim_11062019_proof.pdf | DNB | 969.29 kB | Adobe PDF | View/Open |
Kim_11062019_supplementary_data.pdf | DNB | 547.07 kB | Adobe PDF | View/Open |
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