Unraveling the NALP-3/IL-1beta inflammasome: a big lesson from a small mutation.
Cytokine-mediated inflammation is a target for novel therapies as well as for fundamental research. A single amino acid mutation in the NALP-3 gene controlling the activation of caspase-1 results in increased processing of the inactive IL-1beta precursor and release of the active cytokine. Blocking IL-1 receptors arrests inflammation in humans with the mutation.
Dinarello
Charles A
CA
University Colorado Health Sciences Center, Division of Infectious Diseases, B168, 4200 East Ninth Avenue, Denver, CO 80262, USA.
D001327:Autoimmune Diseases / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism*; D046911:Macromolecular Substances; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011498:Protein Precursors / Q000378:metabolism*
D002352:Carrier Proteins; D007375:Interleukin-1; D046911:Macromolecular Substances; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D011498:Protein Precursors; C043830:interleukin 1 precursor; D020170:Caspase 1