title: Inflammasome-independent regulation of IL-1-family cytokines.
abstract: Induction, production, and release of proinflammatory cytokines are essential steps to establish an effective host defense. Cytokines of the interleukin-1 (IL-1) family induce inflammation and regulate T lymphocyte responses while also displaying homeostatic and metabolic activities. With the exception of the IL-1 receptor antagonist, all IL-1 family cytokines lack a signal peptide and require proteolytic processing into an active molecule. One such unique protease is caspase-1, which is activated by protein platforms called the inflammasomes. However, increasing evidence suggests that inflammasomes and caspase-1 are not the only mechanism for processing IL-1 cytokines. IL-1 cytokines are often released as precursors and require extracellular processing for activity. Here we review the inflammasome-independent enzymatic processes that are able to activate IL-1 cytokines, paying special attention to neutrophil-derived serine proteases, which subsequently induce inflammation and modulate host defense. The inflammasome-independent processing of IL-1 cytokines has important consequences for understanding inflammatory diseases, and it impacts the design of IL-1-based modulatory therapies.
authors.affiliation: Department of Internal Medicine.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Frank L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004198:Disease Susceptibility; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D007375:Interleukin-1
keywords: IL-1β; caspase-1; host defense; inflammasome-independent; serine proteases