Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages.
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.
Netea
Mihai G
MG
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA. m.netea@aig.umcn.nl
Nold-Petry
Claudia A
CA
Nold
Marcel F
MF
Joosten
Leo A B
LA
Opitz
Bastian
B
van der Meer
Jonathan H M
JH
van de Veerdonk
Frank L
FL
Ferwerda
Gerben
G
Heinhuis
Bas
B
Devesa
Isabel
I
Funk
C Joel
CJ
Mason
Robert J
RJ
Kullberg
Bart Jan
BJ
Rubartelli
Anna
A
van der Meer
Jos W M
JW
Dinarello
Charles A
CA
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
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