Abstract
Interleukin-1β (IL-1β) secretion downstream of Toll-like receptor (TLR) activation is tightly controlled at the transcriptional and post-translational levels. NLRP3 inflammasome is involved in the maturation of pro-IL-1β, with NLRP3 expression identified as the limiting factor for inflammasome activation. Previously, we had demonstrated that the zinc-finger protein GFI1 inhibits pro-IL-1β transcription. Here, we show that GFI1 inhibits NLRP3 inflammasome activation and IL-1β secretion in macrophages. GFI1 suppressed Nlrp3 transcription via two mechanisms: (1) by binding to the Gli-responsive element 1 (GRE1) in the Nlrp3 promoter; and (2) by antagonizing the nuclear factor-κB (NF-κB) transcriptional activity. Thus, GFI1 negatively regulates TLR-mediated IL-1β production at both transcriptional and post-translational levels.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Base Sequence
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Carrier Proteins / genetics*
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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Inflammasomes / metabolism*
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Interleukin-1beta / metabolism
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Macrophages / metabolism*
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Mice
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NLR Family, Pyrin Domain-Containing 3 Protein
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Promoter Regions, Genetic / genetics
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Protein Structure, Tertiary
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Toll-Like Receptors / metabolism
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Transcription Factor RelA / metabolism
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Transcription Factors / chemistry
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Transcription Factors / metabolism*
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Transcription, Genetic
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Gfi1 protein, mouse
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Inflammasomes
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Interleukin-1beta
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nlrp3 protein, mouse
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Toll-Like Receptors
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Transcription Factor RelA
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Transcription Factors