ATP-citrate lyase is essential for macrophage inflammatory response.
Growing evidence suggests that energy metabolism and inflammation are closely linked and that cross-talk between these processes is fundamental to the pathogenesis of many human diseases. However, the molecular mechanisms underlying these observations are still poorly understood. Here we describe the key role of ATP-citrate lyase (ACLY) in inflammation. We find that ACLY mRNA and protein levels markedly and quickly increase in activated macrophages. Importantly, ACLY activity inhibition as well as ACLY gene silencing lead to reduced nitric oxide, reactive oxygen species and prostaglandin E2 inflammatory mediators. In conclusion, we present a direct role for ACLY in macrophage inflammatory metabolism.
Department of Science, University of Basilicata, 85100 Potenza, Italy. Electronic address: vittoria.infantino@unibas.it.
Vittoria
V
Infantino
Vito
V
Iacobazzi
Ferdinando
F
Palmieri
Alessio
A
Menga
D001275:ATP Citrate (pro-S)-Lyase / Q000235:genetics* / Q000276:immunology*; D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D015232:Dinoprostone / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation
D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D001275:ATP Citrate (pro-S)-Lyase; D015232:Dinoprostone
ATP-citrate lyase; Immunometabolism; Inflammation; Nitric oxide; Prostaglandin E2; Reactive oxygen species