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

• Published in: Blood Vol. 113; no. 10; pp. 2324 - 2335
• Main Authors: Netea, Mihai G., Nold-Petry, Claudia A., Nold, Marcel F., Joosten, Leo A.B., Opitz, Bastian, van der Meer, Jonathan H.M., van de Veerdonk, Frank L., Ferwerda, Gerben, Heinhuis, Bas, Devesa, Isabel, Funk, C. Joel, Mason, Robert J., Kullberg, Bart Jan, Rubartelli, Anna, van der Meer, Jos W.M., Dinarello, Charles A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 05.03.2009; Americain Society of Hematology; American Society of Hematology
• Series: Phagocytes, Granulocytes, and Myelopoiesis
• Subjects: Biological and medical sciences; Hematologic and hematopoietic diseases; Medical sciences; Phagocytes, Granulocytes, and Myelopoiesis; Interleukin 1β; Hematology; Monocyte; Cytokine; Macrophage
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-03-146720

The processing of pro-interleukin-1β depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1β (IL-1β). Here we demonstrate that human blood monocytes release processed IL-1β 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-1β solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1β production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation.