title: Canonical and non-canonical effects of the NLRP3 inflammasome in kidney inflammation and fibrosis.
abstract: NLRP-3 inflammasome is one of several intracellular danger recognition platforms that integrates infectious or non-infectious types of danger into the expression of pro-inflammatory cytokines to set-up inflammation for danger control. NLRP3 activation induces three types of caspase-1-mediated responses: secretion of IL-1beta, secretion of IL-18 and a programmed form of cell death, referred to as pyroptosis. Similar to the well-documented impact of Toll-like receptor-driven danger signalling in kidney disease, evolving data now suggest a similar involvement of the NLRP3 inflammasome in renal inflammation. Here, we discuss the accumulating data on NLRP3 in the kidney: its IL-1beta and IL-18-dependent 'canonical' effects and the current evidence for its 'non-canonical' effects, e.g. in tumor growth factor (TGF)-beta signalling, epithelial-mesenchymal transition and fibrosis. Research in this area will certainly uncover yet unknown aspects of danger signalling in the kidney and how it drives renal inflammation and immunopathology.
authors.affiliation: Renal Division, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig Maximilians Universität, München-Innenstadt, Munich, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Lorenz
authors.forename: Murthy N
authors.initials: MN
authors.lastname: Darisipudi
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D058847:Inflammasomes / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000473:pathology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D014552:Urinary Tract Infections / Q000503:physiopathology
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D020170:Caspase 1
keywords: crystal nephropathy; dendritic cells; glomerulonephritis; macrophages; tubular injury