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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Carrier Proteins / metabolism
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Caspase 10
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Caspase 8
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Caspase 9
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Caspases / metabolism*
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Cell Separation
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Cell Survival
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Dendritic Cells / enzymology*
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Dose-Response Relationship, Drug
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Enzyme Activation
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Escherichia coli / metabolism
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Flow Cytometry
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Humans
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Intracellular Signaling Peptides and Proteins*
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Lipopolysaccharides / metabolism*
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Mitogen-Activated Protein Kinases / metabolism
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Peptides / chemistry
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Poly(ADP-ribose) Polymerases / metabolism
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Protein Biosynthesis
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Time Factors
Substances
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CASP8 and FADD-Like Apoptosis Regulating Protein
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CFLAR protein, human
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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Lipopolysaccharides
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Peptides
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Poly(ADP-ribose) Polymerases
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Mitogen-Activated Protein Kinases
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CASP8 protein, human
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CASP9 protein, human
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Caspase 10
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Caspase 8
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Caspase 9
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Caspases
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CASP10 protein, human