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

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

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

dc.contributor.author	Molagoda, Ilandarage Menu Neelaka
dc.contributor.author	Lee, Seunghun
dc.contributor.author	Jayasooriya, Rajapaksha Gedara Prasad Tharanga
dc.contributor.author	Jin, Cheng-Yung
dc.contributor.author	Choi, Yung Hyun
dc.contributor.author	Kim, Gi-Young
dc.date.accessioned	2020-02-12T10:00:22Z
dc.date.available	2020-02-12T10:00:22Z
dc.date.issued	2019-06-11
dc.description.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.	en
dc.identifier.issn	1611-2156
dc.identifier.uri	http://hdl.handle.net/2003/38561
dc.identifier.uri	http://dx.doi.org/10.17877/DE290R-20480
dc.language.iso	en
dc.relation.ispartofseries	EXCLI Journal;Vol. 18 2019
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	Deoxynivalenol	en
dc.subject	IL-1 β	en
dc.subject	Nuclear factor- κ B	en
dc.subject	Inflammasome	en
dc.subject.ddc	610
dc.title	Deoxynivalenol enhances IL-1ß expression in BV2 microglial cells through activation of the NF-κB pathway and the ASC/NLRP3 inflammasome	en
dc.type	Text
dc.type.publicationtype	article
dcterms.accessRights	open access
eldorado.dnb.zdberstkatid	2132560-1
eldorado.secondarypublication	true