Febuxostat, a Xanthine Oxidoreductase Inhibitor, Decreases NLRP3-dependent Inflammation in Macrophages by Activating the Purine Salvage Pathway and Restoring Cellular Bioenergetics.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_7553638C2E17
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Febuxostat, a Xanthine Oxidoreductase Inhibitor, Decreases NLRP3-dependent Inflammation in Macrophages by Activating the Purine Salvage Pathway and Restoring Cellular Bioenergetics.
Périodique
Scientific reports
Auteur⸱e⸱s
Nomura J., Kobayashi T., So A., Busso N.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
21/11/2019
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
17314
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome mediates caspase-1 activation and IL-1β processing and is implicated in autoinflammatory as well as other chronic inflammatory diseases. Recent studies have demonstrated that xanthine oxidoreductase (XOR) inhibition attenuated IL-1β secretion in activated macrophages, but the detailed mechanism of inhibition remains unclear. In this study, we report that febuxostat, an inhibitor of XOR, suppressed NLRP3 inflammasome-mediated IL-1β secretion and cell death by two mechanisms: in a mitochondrial ROS (mitoROS)-dependent and mitoROS-independent manner. MitoROS-independent effects of febuxostat were mediated by an increase of intracellular ATP and improved mitochondrial energetics via the activation of purine salvage pathway. Our findings suggest that cellular bioenergetics are important in regulating NLRP3 activation, and XOR inhibition may be clinically relevant in NLRP3-related inflammatory diseases.
Mots-clé
Animals, Anti-Inflammatory Agents/pharmacology, Anti-Inflammatory Agents/therapeutic use, Cells, Cultured, Energy Metabolism/drug effects, Energy Metabolism/immunology, Febuxostat/pharmacology, Febuxostat/therapeutic use, Humans, Inflammasomes/drug effects, Inflammasomes/immunology, Inflammasomes/metabolism, Inflammation/drug therapy, Inflammation/immunology, Macrophages/drug effects, Macrophages/immunology, Macrophages/metabolism, Mice, Mitochondria/drug effects, Mitochondria/metabolism, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, Primary Cell Culture, Purines/metabolism, Reactive Oxygen Species/metabolism, Xanthine Dehydrogenase/antagonists & inhibitors, Xanthine Dehydrogenase/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/12/2019 15:41
Dernière modification de la notice
23/04/2024 6:12
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