Nucleotide-Binding Oligomerization Domain-Like Receptors and Inflammasomes in the Pathogenesis of Non-Microbial Inflammation and Diseases
Open Access
- 4 November 2011
- journal article
- review article
- Published by S. Karger AG in Journal of Innate Immunity
- Vol. 4 (1), 16-30
- https://doi.org/10.1159/000334247
Abstract
The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) or nucleotide-binding domain leucine-rich repeat-containing family of genes plays an important role in the development of innate immune responses. Some family members are known to form multiprotein complexes known as inflammasomes that regulate the processing and secretion of proinflammatory mediators, such as interleukin-1β and interleukin-18. Activity of the inflammasome is triggered not only by microbial infection, but also by a wide range of both exogenous and endogenous noninfectious stimuli. Consequently, the dysregulation of inflammasome activity is associated with numerous proinflammatory, non-microbial human diseases. The discovery of NLRP3 gene mutations in autoinflammatory diseases such as Muckle-Wells syndrome has led to the association of NLRs in the pathogenesis of many non-microbial diseases that include arthritis, neurodegenerative disorders, metabolic disorders (obesity and diabetes), cardiovascular disease (atherosclerosis, myocardial infarction), inflammatory bowel disease, kidney disease and hypersensitivity dermatitis. A number of NLRs are also associated with human disease in the absence of inflammasome activity, suggesting additional roles for NLRs in the regulation of inflammation and disease. This review serves to provide a summary of NLR-associated diseases and, where possible, the mechanisms behind the associations.Keywords
This publication has 99 references indexed in Scilit:
- Inflammasome-Dependent Release of the Alarmin HMGB1 in EndotoxemiaThe Journal of Immunology, 2010
- Neuronal apoptosis inhibitory protein, NAIP, is an inhibitor of procaspase-9The International Journal of Biochemistry & Cell Biology, 2010
- The InflammasomesCell, 2010
- NLRP3 (NALP3, Cryopyrin) Facilitates In Vivo Caspase-1 Activation, Necrosis, and HMGB1 Release via Inflammasome-Dependent and -Independent PathwaysThe Journal of Immunology, 2009
- Cryopyrinopathies: update on pathogenesis and treatmentNature Clinical Practice Rheumatology, 2008
- The NLR Gene Family: A Standard NomenclatureImmunity, 2008
- Active Caspase-1 Is a Regulator of Unconventional Protein SecretionCell, 2008
- The Caspase-1 Digestome Identifies the Glycolysis Pathway as a Target during Infection and Septic ShockJournal of Biological Chemistry, 2007
- The InflammasomeMolecular Cell, 2002
- Nitric Oxide Induces Thymocyte Apoptosis Via a Caspase-1-Dependent MechanismThe Journal of Immunology, 2000