title: The transcription factor GFI1 negatively regulates NLRP3 inflammasome activation in macrophages.
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.
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Liuluan
authors.initials: L
authors.lastname: Zhu
authors.forename: Qingcai
authors.initials: Q
authors.lastname: Meng
authors.forename: Shuntao
authors.initials: S
authors.lastname: Liang
authors.forename: Yaluan
authors.initials: Y
authors.lastname: Ma
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Guoli
authors.initials: G
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D051193:Toll-Like Receptors / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D051193:Toll-Like Receptors; D051996:Transcription Factor RelA; D014157:Transcription Factors