The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.

Details

Serval ID
serval:BIB_14E323F787D3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.
Journal
Journal of the American Society of Nephrology
Author(s)
Vilaysane A., Chun J., Seamone M.E., Wang W., Chin R., Hirota S., Li Y., Clark S.A., Tschopp J., Trpkov K., Hemmelgarn B.R., Beck P.L., Muruve D.A.
ISSN
1533-3450[electronic], 1046-6673[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
21
Number
10
Pages
1732-1744
Language
english
Abstract
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.
Keywords
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
Yes
Create date
07/09/2010 15:18
Last modification date
20/08/2019 12:43
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