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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Date
2019-06-11
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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.
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Keywords
Deoxynivalenol, IL-1 β, Nuclear factor- κ B, Inflammasome