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Acute Iron Deprivation Reprograms Human Macrophage Metabolism and Reduces Inflammation In Vivo.
Pereira, Marie; Chen, Tai-Di; Buang, Norzawani; Olona, Antoni; Ko, Jeong-Hun; Prendecki, Maria; Costa, Ana S H; Nikitopoulou, Efterpi; Tronci, Laura; Pusey, Charles D; Cook, H Terence; McAdoo, Stephen P; Frezza, Christian; Behmoaras, Jacques.
Afiliación
  • Pereira M; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK.
  • Chen TD; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK; Department of Anatomic Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Buang N; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK.
  • Olona A; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK.
  • Ko JH; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK.
  • Prendecki M; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK.
  • Costa ASH; Medical Research Council Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Nikitopoulou E; Medical Research Council Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Tronci L; Medical Research Council Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Pusey CD; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK.
  • Cook HT; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK.
  • McAdoo SP; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK.
  • Frezza C; Medical Research Council Cancer Unit, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Behmoaras J; Centre for Inflammatory Disease, Imperial College London, London W12 0NN, UK. Electronic address: jacques.behmoaras@imperial.ac.uk.
Cell Rep ; 28(2): 498-511.e5, 2019 07 09.
Article en En | MEDLINE | ID: mdl-31291584
Iron is an essential metal that fine-tunes the innate immune response by regulating macrophage function, but an integrative view of transcriptional and metabolic responses to iron perturbation in macrophages is lacking. Here, we induced acute iron chelation in primary human macrophages and measured their transcriptional and metabolic responses. Acute iron deprivation causes an anti-proliferative Warburg transcriptome, characterized by an ATF4-dependent signature. Iron-deprived human macrophages show an inhibition of oxidative phosphorylation and a concomitant increase in glycolysis, a large increase in glucose-derived citrate pools associated with lipid droplet accumulation, and modest levels of itaconate production. LPS polarization increases the itaconate:succinate ratio and decreases pro-inflammatory cytokine production. In rats, acute iron deprivation reduces the severity of macrophage-dependent crescentic glomerulonephritis by limiting glomerular cell proliferation and inducing lipid accumulation in the renal cortex. These results suggest that acute iron deprivation has in vivo protective effects mediated by an anti-inflammatory immunometabolic switch in macrophages.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Deficiencias de Hierro / Inflamación Límite: Animals / Humans / Male Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Deficiencias de Hierro / Inflamación Límite: Animals / Humans / Male Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos