Histones trigger sterile inflammation by activating the NLRP3 inflammasome.

Détails

ID Serval
serval:BIB_CB5F5DE53CBF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Histones trigger sterile inflammation by activating the NLRP3 inflammasome.
Périodique
European Journal of Immunology
Auteur(s)
Allam R., Darisipudi M.N., Tschopp J., Anders H.J.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
2013
Volume
43
Numéro
12
Pages
3336-3342
Langue
anglais
Résumé
Sterile cell death mediated inflammation is linked to several pathological disorders and involves danger recognition of intracellular molecules released by necrotic cells that activate different groups of innate pattern recognition receptors. Toll-like receptors directly interact with their extrinsic or intrinsic agonists and induce multiple proinflammatory mediators. In contrast, the NLRP3 inflammasome is rather thought to represent a downstream element integrating various indirect stimuli into proteolytic cleavage of interleukin (IL)-1β and IL-18. Here, we report that histones released from necrotic cells induce IL-1β secretion in an NLRP3-ASC-caspase-1-dependent manner. Genetic deletion of NLRP3 in mice significantly attenuated histone-induced IL-1β production and neutrophil recruitment. Furthermore, necrotic cells induced neutrophil recruitment, which was significantly reduced by histone-neutralizing antibodies or depleting extracellular histones via enzymatic degradation. These results identify cytosolic uptake of necrotic cell-derived histones as a triggering mechanism of sterile inflammation, which involves NLRP3 inflammasome activation and IL-1β secretion via oxidative stress.
Mots-clé
Histones, Inflammasome, Interleukin-1, NLRP3, Sterile inflammation
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/01/2014 9:06
Dernière modification de la notice
20/08/2019 15:46
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