ENaC-mediated sodium influx exacerbates NLRP3-dependent inflammation in cystic fibrosis.

Détails

Ressource 1Télécharger: elife-49248-v2.pdf (2516.06 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_106C52DF162A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
ENaC-mediated sodium influx exacerbates NLRP3-dependent inflammation in cystic fibrosis.
Périodique
eLife
Auteur⸱e⸱s
Scambler T., Jarosz-Griffiths H.H., Lara-Reyna S., Pathak S., Wong C., Holbrook J., Martinon F., Savic S., Peckham D., McDermott M.F.
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Statut éditorial
Publié
Date de publication
18/09/2019
Peer-reviewed
Oui
Volume
8
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Cystic Fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective CFTR-mediated chloride and bicarbonate transport, with dysregulation of epithelial sodium channels (ENaC). These changes alter fluid and electrolyte homeostasis and result in an exaggerated proinflammatory response driven, in part, by infection. We tested the hypothesis that NLRP3 inflammasome activation and ENaC upregulation drives exaggerated innate-immune responses in this multisystem disease. We identify an enhanced proinflammatory signature, as evidenced by increased levels of IL-18, IL-1β, caspase-1 activity and ASC-speck release in monocytes, epithelia and serum with CF-associated mutations; these differences were reversed by pretreatment with NLRP3 inflammasome inhibitors and notably, inhibition of amiloride-sensitive sodium (Na <sup>+</sup> ) channels. Overexpression of β-ENaC, in the absence of CFTR dysfunction, increased NLRP3-mediated inflammation, indicating that dysregulated, ENaC-dependent signalling may drive exaggerated inflammatory responses in CF. These data support a role for sodium in modulating NLRP3 inflammasome activation.
Mots-clé
Cell Line, Cystic Fibrosis/pathology, Epithelial Sodium Channels/metabolism, Humans, Immunity, Innate, Inflammation/pathology, NLR Family, Pyrin Domain-Containing 3 Protein/metabolism, Sodium/metabolism, NLRP3, autoinflammation, cystic fibrosis, human, human biology, immunology, inflammasome, inflammation, medicine, potassium transport, sodium transport
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/09/2019 22:17
Dernière modification de la notice
07/02/2020 7:19
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