Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages

Mihea G Netea, Claudia Annelie Nold-Petry, Marcel F Nold, Leo A B Joosten, Bastian Opitz, Jonathan H M van der Meer, Frank L van de Veerdonk, Gerben Ferwerda, Bas Heinhuis, Isabel Devesa, C Joel Joel Funk, Robert J Mason, Bart Jan Kullberg, Anna Rubartelli, Jos W M van der Meer, Charles A Dinarello

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600 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)2324 - 2335
Number of pages12
Issue number10
Publication statusPublished - 2009
Externally publishedYes

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