A caspaselike activity is triggered by LPS and is required for survival of human dendritic cells.
Franchi, Luigi ; Condo, Ivano ; Tomassini, Barbara ; et al. ; - ASI Sponsor
Oct - 2003
ISSN : 0006-4971 ;
journal : Blood

Issue : 8
type: Article Journal

Abstract
Bacterial endotoxin (lipopolysaccharide [LPS]) is a potent inducer of human dendritic cell (DC) maturation and survival. Here we show that immature DCs exposed to LPS trigger an early and sustained caspase-like activity, which can be blocked by zVAD (z-Val-Ala-Asp), in the absence of detectable caspase 8 and caspase 10 activation, or poly(ADP-ribose) polymerase (PARP)-cleaving activity. Preventing LPS-induced caspase-like activation in DC results in massive cell death. Importantly, triggering of the caspase-like activity is required for LPS-induced activation of extracellular signal-regulated kinases (ERKs) and for LPS-induced up-regulation of cFLIP (Fas-associating protein with death domain-like interleukin-1 beta-converting enzyme [FLICE]-like inhibitory protein). Therefore, a caspase-dependent pathway initiated by LPS controls survival of human DCs.

keywords : ASI - Sponsor,Blotting,CASP8 and FADD-Like Apoptosis Regulating Protein,Carrier Proteins,Carrier Proteins: metabolism,Caspase 10,Caspase 8,Caspase 9,Caspases,Caspases: metabolism,Cell Separation,Cell Survival,Dendritic Cells,Dendritic Cells: enzymology,Dose-Response Relationship,Drug,Enzyme Activation,Escherichia coli,Escherichia coli: metabolism,Flow Cytometry,Humans,Intracellular Signaling Peptides and Proteins,Lipopolysaccharides,Lipopolysaccharides: metabolism,Mitogen-Activated Protein Kinases,Mitogen-Activated Protein Kinases: metabolism,Peptides,Peptides: chemistry,Poly(ADP-ribose) Polymerases,Poly(ADP-ribose) Polymerases: metabolism,Protein Biosynthesis,Time Factors,Western