A caspaselike activity is triggered by LPS and is required for survival of human dendritic cells.
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.
Franchi
Luigi
L
Laboratory of Immunology and Signal Transduction, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy.
Condò
Ivano
I
Tomassini
Barbara
B
Nicolò
Chiara
C
Testi
Roberto
R
D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000378:metabolism; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002469:Cell Separation; D002470:Cell Survival; D003713:Dendritic Cells / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004926:Escherichia coli / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014176:Protein Biosynthesis; D013997:Time Factors
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D010455:Peptides; D011065:Poly(ADP-ribose) Polymerases; D020928:Mitogen-Activated Protein Kinases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; C506438:CASP10 protein, human