title: Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders.
abstract: Recent studies have indicated that the regulation of innate immunity and energy metabolism are connected together through an antagonistic crosstalk between NF-κB and SIRT1 signaling pathways. NF-κB signaling has a major role in innate immunity defense while SIRT1 regulates the oxidative respiration and cellular survival. However, NF-κB signaling can stimulate glycolytic energy flux during acute inflammation, whereas SIRT1 activation inhibits NF-κB signaling and enhances oxidative metabolism and the resolution of inflammation. SIRT1 inhibits NF-κB signaling directly by deacetylating the p65 subunit of NF-κB complex. SIRT1 stimulates oxidative energy production via the activation of AMPK, PPARα and PGC-1α and simultaneously, these factors inhibit NF-κB signaling and suppress inflammation. On the other hand, NF-κB signaling down-regulates SIRT1 activity through the expression of miR-34a, IFNγ, and reactive oxygen species. The inhibition of SIRT1 disrupts oxidative energy metabolism and stimulates the NF-κB-induced inflammatory responses present in many chronic metabolic and age-related diseases. We will examine the molecular mechanisms of the antagonistic signaling between NF-κB and SIRT1 and describe how this crosstalk controls inflammatory process and energy metabolism. In addition, we will discuss how disturbances in this signaling crosstalk induce the appearance of chronic inflammation in metabolic diseases.
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Suuronen
authors.forename: Johanna
authors.initials: J
authors.lastname: Ojala
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
mesh_terms: D004734:Energy Metabolism / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: AGRP; AMP-activated protein kinase; AMPK; AP-1; Aging; B-cell lymphoma/leukemia-10; BCL10; CIITA; DHA; E2F1; EPA; ERK; Forkhead box O protein; FoxO; GAPDH; HIC1; HIF; IAP-2; IFN-γ; IKK; IL; Inflammation; IκBα; JAK; Janus kinase; LKB1; LPS; M1; M2; MCP-1; Metabolic disease; NAD; NAMPT; NF-κB; NLR; NOS; PARP-1; PDK4; PGC-1α; PHD; PPAR; ROS; SF1; SIRT1; STAT; SUMO; TGFβ; TLR; TNFα; Toll-like receptor; UTR; activator protein-1; agouti-related protein; alternatively activated anti-inflammatory macrophage; class II, major histocompatibility complex, transactivator; classically activated proinflammatory macrophage; docosahexaenoic acid; eicosapentaenoic acid; extracellular signal-regulated kinase; glyceraldehyde 3-phosphate dehydrogenase; hypermethylated in cancer-1; hypoxia-inducible factor; inhibitor of apoptosis-2; inhibitor of κB protein-α; inhibitory-κB kinase; interferon-γ; interleukin; lipopolysaccharide; miR; microRNAs; monocyte chemotactic protein-1; nicotinamide adenine dinucleotide; nicotinamide mononucleotide adenylyltransferase; nitric oxide synthase; nuclear factor-κB; nucleotide-binding domain leucine-rich repeat-containing receptor; peroxisome proliferator-activated receptor; peroxisome proliferator-activated receptor-γ coactivator-1α; poly(ADP-ribose) polymerase-1; prolyl-hydroxylase domain-containing protein; pyruvate dehydrogenase kinase 4; reactive oxygen species; serine/threonine kinase 11; signal transducer and activator of transcription; silent information regulator 1; small ubiquitin-like modifier; steroidogenic factor 1; transcription factor E2F1; transforming growth factor β; tumor necrosis factor-α; untranslated region