Canonical and non-canonical effects of the NLRP3 inflammasome in kidney inflammation and fibrosis

Nephrol Dial Transplant. 2014 Jan;29(1):41-8. doi: 10.1093/ndt/gft332. Epub 2013 Sep 11.

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.

Keywords: crystal nephropathy; dendritic cells; glomerulonephritis; macrophages; tubular injury.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Carrier Proteins / physiology*
  • Caspase 1 / metabolism
  • Cytokines / metabolism
  • Epithelial-Mesenchymal Transition / physiology
  • Fibrosis
  • Humans
  • Inflammasomes / physiology*
  • Inflammation / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Kidney / pathology
  • Kidney Diseases / pathology*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Urinary Tract Infections / physiopathology

Substances

  • Carrier Proteins
  • Cytokines
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Caspase 1