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

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 stimula...

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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
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Abstract	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.
AbstractList	Abstract 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. 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.
Author	Opitz, Bastian van der Meer, Jonathan H.M. Nold, Marcel F. van der Meer, Jos W.M. Ferwerda, Gerben Kullberg, Bart Jan Funk, C. Joel Netea, Mihai G. Heinhuis, Bas Dinarello, Charles A. Nold-Petry, Claudia A. van de Veerdonk, Frank L. Joosten, Leo A.B. Devesa, Isabel Rubartelli, Anna Mason, Robert J.
Author_xml	– sequence: 1 givenname: Mihai G. surname: Netea fullname: Netea, Mihai G. email: m.netea@aig.umcn.nl organization: Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver – sequence: 2 givenname: Claudia A. surname: Nold-Petry fullname: Nold-Petry, Claudia A. organization: Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver – sequence: 3 givenname: Marcel F. surname: Nold fullname: Nold, Marcel F. organization: Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver – sequence: 4 givenname: Leo A.B. surname: Joosten fullname: Joosten, Leo A.B. organization: Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands – sequence: 5 givenname: Bastian surname: Opitz fullname: Opitz, Bastian organization: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany – sequence: 6 givenname: Jonathan H.M. surname: van der Meer fullname: van der Meer, Jonathan H.M. organization: Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver – sequence: 7 givenname: Frank L. surname: van de Veerdonk fullname: van de Veerdonk, Frank L. organization: Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands – sequence: 8 givenname: Gerben surname: Ferwerda fullname: Ferwerda, Gerben organization: Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands – sequence: 9 givenname: Bas surname: Heinhuis fullname: Heinhuis, Bas organization: Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands – sequence: 10 givenname: Isabel surname: Devesa fullname: Devesa, Isabel organization: Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands – sequence: 11 givenname: C. Joel surname: Funk fullname: Funk, C. Joel organization: Department of Medicine, National Jewish Medical and Research Center, Denver, CO – sequence: 12 givenname: Robert J. surname: Mason fullname: Mason, Robert J. organization: Department of Medicine, National Jewish Medical and Research Center, Denver, CO – sequence: 13 givenname: Bart Jan surname: Kullberg fullname: Kullberg, Bart Jan organization: Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands – sequence: 14 givenname: Anna surname: Rubartelli fullname: Rubartelli, Anna organization: Department of Experimental Oncology E (Cell Biology), Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy – sequence: 15 givenname: Jos W.M. surname: van der Meer fullname: van der Meer, Jos W.M. organization: Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands – sequence: 16 givenname: Charles A. surname: Dinarello fullname: Dinarello, Charles A. organization: Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver
BackLink	http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21207221$$DView record in Pascal Francis
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Keywords	Interleukin 1β Hematology Monocyte Cytokine Macrophage
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Publisher	Elsevier Inc Americain Society of Hematology American Society of Hematology
Publisher_xml	– name: Elsevier Inc – name: Americain Society of Hematology – name: American Society of Hematology
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Snippet	The processing of pro-interleukin-1β depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate... Abstract The processing of pro-interleukin-1β depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can...
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SubjectTerms	Biological and medical sciences Hematologic and hematopoietic diseases Medical sciences Phagocytes, Granulocytes, and Myelopoiesis
Title	Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages
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