title: Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages.
abstract: The processing of pro-interleukin-1beta depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1beta (IL-1beta). Here we demonstrate that human blood monocytes release processed IL-1beta after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine triphosphate. The constitutive activation of caspase-1 depends on the inflammasome components, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and NALP3, but in monocytes caspase-1 activation is uncoupled from pathogen-associated molecular pattern recognition. In contrast, macrophages are unable to process and release IL-1beta solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1beta production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation.
authors.affiliation: Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA. m.netea@aig.umcn.nl
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Nold-Petry
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Nold
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
authors.forename: Jonathan H M
authors.initials: JH
authors.lastname: van der Meer
authors.forename: Frank L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.forename: Gerben
authors.initials: G
authors.lastname: Ferwerda
authors.forename: Bas
authors.initials: B
authors.lastname: Heinhuis
authors.forename: Isabel
authors.initials: I
authors.lastname: Devesa
authors.forename: C Joel
authors.initials: CJ
authors.lastname: Funk
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mason
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Anna
authors.initials: A
authors.lastname: Rubartelli
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D053468:CARD Signaling Adaptor Proteins; D016466:CHO Cells; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D020170:Caspase 1