title: The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.
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.
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Akosua
authors.initials: A
authors.lastname: Vilaysane
authors.forename: Justin
authors.initials: J
authors.lastname: Chun
authors.forename: Mark E
authors.initials: ME
authors.lastname: Seamone
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.forename: Rick
authors.initials: R
authors.lastname: Chin
authors.forename: Simon
authors.initials: S
authors.lastname: Hirota
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Clark
authors.forename: Jurg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Kiril
authors.initials: K
authors.lastname: Trpkov
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
authors.forename: Paul L
authors.initials: PL
authors.lastname: Beck
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Muruve
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009393:Nephritis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D012333:RNA, Messenger