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PMID: 17047155 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Caspase-8 prevents sustained activation of NF-kappaB in monocytes undergoing macrophagic differentiation.

Blood ·Vol. 109 ·No. 4 ·2007-02-15 ·Pages 1442-50

Rébé C, Cathelin S, Launay S, Filomenko R, Prévotat L, L'Ollivier C, Gyan E, Micheau O, Grant S, Dubart-Kupperschmitt A, Fontenay M, Solary E

Abstract

Caspases have demonstrated several nonapoptotic 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. On 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-kappaB activation, and activates downstream caspases. Together these data identify a role for caspase-8 in monocytes undergoing macrophagic differentiation, that is, the enzyme activated in an atypical complex down-regulates NF-kappaB activity through RIP1 cleavage.

MeSH Terms
Caspase 8/metabolism,physiology Cell Differentiation Cell Line, Tumor Fas-Associated Death Domain Protein/metabolism Humans Macrophage Colony-Stimulating Factor/pharmacology Macrophages/cytology Monocytes/cytology NF-kappa B/metabolism Nuclear Pore Complex Proteins/metabolism RNA-Binding Proteins/metabolism
Chemicals
AGFG1 protein, human FADD protein, human Fas-Associated Death Domain Protein NF-kappa B Nuclear Pore Complex Proteins RNA-Binding Proteins Macrophage Colony-Stimulating Factor Caspase 8
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Rébé Cédric
Institut National de la Santé et de la Recherche Médicale (INSERM) U517, Dijon, France.
Cathelin Séverine
Launay Sophie
Filomenko Rodolphe
Prévotat Laurent
L'Ollivier Coralie
Gyan Emmanuel
Micheau Olivier
Grant Steven
Dubart-Kupperschmitt Anne
Fontenay Michaëla
Solary Eric
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-03-011585
Published
2007-02-15
Epub
2006-00-17
Pages
1442-50
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2492986
Subset
IM
External Links
PubMed source DOI: 10.1182/blood-2006-03-011585 PMC Full Text View journal details
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