Intracellular ATP Decrease Mediates NLRP3 Inflammasome Activation upon Nigericin and Crystal Stimulation.

Détails

ID Serval
serval:BIB_975C46EE3B4B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Intracellular ATP Decrease Mediates NLRP3 Inflammasome Activation upon Nigericin and Crystal Stimulation.
Périodique
Journal of Immunology
Auteur(s)
Nomura J., So A., Tamura M., Busso N.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
195
Numéro
12
Pages
5718-5724
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Activation of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome initiates an inflammatory response, which is associated with host defense against pathogens and the progression of chronic inflammatory diseases such as gout and atherosclerosis. The NLRP3 inflammasome mediates caspase-1 activation and subsequent IL-1β processing in response to various stimuli, including extracellular ATP, although the roles of intracellular ATP (iATP) in NLRP3 activation remain unclear. In this study, we found that in activated macrophages artificial reduction of iATP by 2-deoxyglucose, a glycolysis inhibitor, caused mitochondrial membrane depolarization, leading to IL-1β secretion via NLRP3 and caspase-1 activation. Additionally, the NLRP3 activators nigericin and monosodium urate crystals lowered iATP through K(+)- and Ca(2+)-mediated mitochondrial dysfunction, suggesting a feedback loop between iATP loss and lowering of mitochondrial membrane potential. These results demonstrate the fundamental roles of iATP in the maintenance of mitochondrial function and regulation of IL-1β secretion, and they suggest that maintenance of the intracellular ATP pools could be a strategy for countering NLRP3-mediated inflammation.
Mots-clé
Adenosine Triphosphate/metabolism, Animals, Caspase 1/metabolism, Cells, Cultured, Deoxyglucose/metabolism, Humans, Inflammasomes/immunology, Inflammation/immunology, Interleukin-1beta/metabolism, Intracellular Space, Macrophages/immunology, Mice, Inbred C57BL, Nerve Tissue Proteins/metabolism, Nigericin/metabolism, Uric Acid/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/12/2015 11:41
Dernière modification de la notice
20/08/2019 14:59
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