UVB-induced apoptosis of human dendritic cells: contribution by caspase-dependent and caspase-independent pathways.
Dendritic cells (DCs) play a central role in the initiation and regulation of the immune response. The modalities by which DCs are committed to undergo apoptosis are poorly defined. Here it is shown that, unlike death receptor ligands, UVB radiation triggers apoptosis of human DCs very efficiently. UVB exposure is followed by the activation of caspases 8, 9, and 3, by the loss of mitochondrial transmembrane potential (deltaPsim), and by cellular and nuclear fragmentation. Caspase inhibitors substantially prevented the occurrence of cellular and nuclear fragmentation but had no effect on UVB-induced deltaPsim dissipation. Importantly, mature DCs (MDCs) displayed relative resistance to UVB; UVB-induced caspase activation and apoptosis were substantially delayed compared to immature DCs (IDCs). Resistance correlated with the strong up-regulation of cellular FLIP and bcl2 observed in MDCs compared to IDCs.
Nicolò
C
C
Laboratory of Signal Transduction, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Tomassini
B
B
Rippo
M R
MR
Testi
R
R
D017209:Apoptosis / Q000528:radiation effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D018929:Cell Culture Techniques; D002463:Cell Membrane Permeability / Q000528:radiation effects; D003713:Dendritic Cells / Q000201:enzymology / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D007425:Intracellular Membranes / Q000528:radiation effects; D047908:Intracellular Signaling Peptides and Proteins; D008564:Membrane Potentials / Q000528:radiation effects; D008928:Mitochondria / Q000528:radiation effects / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D014466:Ultraviolet Rays
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases