کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3353395 | 1216854 | 2011 | 14 صفحه PDF | دانلود رایگان |
SummaryPrecise control of myeloid cell activation is required for optimal host defense. However, this activation process must be under exquisite control to prevent uncontrolled inflammation. Herein, we identify the Kruppel-like transcription factor 2 (KLF2) as a potent regulator of myeloid cell activation in vivo. Exposure of myeloid cells to hypoxia and/or bacterial products reduced KLF2 expression while inducing hypoxia inducible factor-1α (HIF-1α), findings that were recapitulated in human septic patients. Myeloid KLF2 was found to be a potent inhibitor of nuclear factor-kappaB (NF-κB)-dependent HIF-1α transcription and, consequently, a critical determinant of outcome in models of polymicrobial infection and endotoxemia. Collectively, these observations identify KLF2 as a tonic repressor of myeloid cell activation in vivo and an essential regulator of the innate immune system.
Graphical AbstractFigure optionsDownload high-quality image (428 K)Download as PowerPoint slideHighlights
► KLF2 deficiency confers a proinflammatory phenotype to myeloid cells
► Myeloid KLF2 deficiency renders animals resistant to polymicrobial infection
► Myeloid KLF2 deficiency renders animals susceptible to endotoxic shock
► KLF2 negatively regulates the NF-κB-HIF-1α axis in macrophages
Journal: - Volume 34, Issue 5, 27 May 2011, Pages 715–728