Premium
The transcription factor GFI1 negatively regulates NLRP3 inflammasome activation in macrophages
Author(s) -
Zhu Liuluan,
Meng Qingcai,
Liang Shuntao,
Ma Yaluan,
Li Rui,
Li Guoli,
Zeng Hui
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.10.025
Subject(s) - inflammasome , transcription factor , microbiology and biotechnology , chemistry , secretion , transcription (linguistics) , caspase 1 , receptor , zinc finger , promoter , biology , gene expression , gene , biochemistry , linguistics , philosophy
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.