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Blood, 5 March 2009, Vol. 113, No. 10, pp. 2324-2335. Prepublished online as a Blood First Edition Paper on December 22, 2008; DOI 10.1182/blood-2008-03-146720. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-03-146720v1 113/10/2324    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Netea, M. G. Articles by Dinarello, C. A. Search for Related Content PubMed PubMed Citation Articles by Netea, M. G. Articles by Dinarello, C. A. Related Collections Immunobiology Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages Mihai G. Netea13, Claudia A. Nold-Petry1,*, Marcel F. Nold1,*, Leo A. B. Joosten2,3, Bastian Opitz4, Jonathan H. M. van der Meer1, Frank L. van de Veerdonk2,3, Gerben Ferwerda2,3, Bas Heinhuis5, Isabel Devesa5, C. Joel Funk6, Robert J. Mason6, Bart Jan Kullberg2,3, Anna Rubartelli7, Jos W. M. van der Meer2,3, and Charles A. Dinarello1 1 Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver; 2 Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; 3 Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands; 4 Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany; 5 Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; 6 Department of Medicine, National Jewish Medical and Research Center, Denver, CO; and 7 Department of Experimental Oncology E (Cell Biology), Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. L. Hailey, S. Li, M. D. 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