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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1442-1450. Prepublished online as a Blood First Edition Paper on October 17, 2006; DOI 10.1182/blood-2006-03-011585. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-03-011585v1 109/4/1442    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rebe, C. Articles by Solary, E. Search for Related Content PubMed PubMed Citation Articles by Rebe, C. Articles by Solary, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 22, 2006 Accepted September 27, 2006 Caspase-8 prevents sustained activation of NF-B in monocytes undergoing macrophagic differentiation Cedric Rebe, Severine Cathelin, Sophie Launay, Rodolphe Filomenko, Laurent Prevotat, Coralie L'Ollivier, Emmanuel Gyan, Olivier Micheau, Steven Grant, Anne Dubart-Kupperschmitt, Michaela Fontenay, and Eric Solary* Institut Nationale de Sante et de Recherche Medicale (INSERM) U517, France Institut Federatif de Recherche (IFR) 100, University of Burgundy, France Ecole Pratique des Hautes Etudes (EPHE), Faculty of Medicine, France Centre Hospitalier Universitaire, France INSERM U567, Institut Cochin, France Dept of Pharmacology & biochemistry, Virginia Commonwealth University, Richmond, VA, United States Dept of Hematology, Cochin Hospital, Paris, France * Corresponding author; email: esolary{at}u-bourgogne.fr. Caspases have demonstrated several non-apoptotic functions including a role in the differentiation of specific cell types. Here, we show that caspase-8 is the upstream enzyme in the proteolytic caspase cascade whose activation is required for the differentiation of peripheral blood monocytes into macrophages. Upon Macrophage Colony Stimulating Factor (M-CSF) exposure, caspase-8 associates with the adaptor protein Fas-Associated Death Domain (FADD), the serine/threonine kinase Receptor-Interacting-Protein 1 (RIP1) and the long isoform of FLICE-inhibitory protein FLIP. Overexpression of FADD accelerates the differentiation process that does not involve any death receptor. Active caspase-8 cleaves RIP1, which prevents sustained NF-B activation, and activates downstream caspases. Altogether, these data identify a role for caspase-8 in monocytes undergoing macrophagic differentiation, i.e. the enzyme activated in an atypical complex down-regulates NF-B activity through RIP1 cleavage. 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