کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2047563 1073989 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The transcription factor GFI1 negatively regulates NLRP3 inflammasome activation in macrophages
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
The transcription factor GFI1 negatively regulates NLRP3 inflammasome activation in macrophages
چکیده انگلیسی


• Gfi1 modulates NLRP3 inflammasome-mediated IL-1β production in macrophages.
• Gfi1 inhibits Nlrp3 transcription through direct binding to promoter DNA.
• Gfi1 inhibits Nlrp3 transcription indirectly by interfering with NF-κB activity.
• SNAG domain and zinc-finger motif of Gfi1 are indispensable for regulation of Nlrp3.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 588, Issue 23, 28 November 2014, Pages 4513–4519
نویسندگان
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