The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.
Détails
ID Serval
serval:BIB_14E323F787D3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.
Périodique
Journal of the American Society of Nephrology
ISSN
1533-3450[electronic], 1046-6673[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
21
Numéro
10
Pages
1732-1744
Langue
anglais
Résumé
Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1β and IL-18, play a role in CKD, but their regulation during renal injury is unknown. Here, we analyzed the processing of caspase-1, IL-1β, and IL-18 after unilateral ureteral obstruction (UUO) in mice, which suggested activation of the Nlrp3 inflammasome during renal injury. Compared with wild-type mice, Nlrp3(-/-) mice had less tubular injury, inflammation, and fibrosis after UUO, associated with a reduction in caspase-1 activation and maturation of IL-1β and IL-18; these data confirm that the Nlrp3 inflammasome upregulates these cytokines in the kidney during injury. Bone marrow chimeras revealed that Nlrp3 mediates the injurious/inflammatory processes in both hematopoietic and nonhematopoietic cellular compartments. In tissue from human renal biopsies, a wide variety of nondiabetic kidney diseases exhibited increased expression of NLRP3 mRNA, which correlated with renal function. Taken together, these results strongly support a role for NLRP3 in renal injury and identify the inflammasome as a possible therapeutic target in the treatment of patients with progressive CKD.
Mots-clé
Animals, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cells, Cultured, Fibrosis, Humans, Kidney/pathology, Male, Mice, Mice, Inbred C57BL, Nephritis/metabolism, RNA, Messenger/metabolism, Renal Insufficiency, Chronic/metabolism, Ureteral Obstruction/metabolism, Ureteral Obstruction/pathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/09/2010 16:18
Dernière modification de la notice
20/08/2019 13:43