Ceramide catabolism critically controls survival of human dendritic cells.
The regulation of dendritic cell (DC) survival is crucial for the modulation of adaptive immunity. Ceramide is a lipid mediator of the stress response, which accumulates intracellularly during DC differentiation. We found that ceramide levels are tightly regulated in human DCs and that the pharmacological inhibition of enzymes responsible for ceramide catabolism, such as ceramidases and sphingosine kinases, sensitizes DCs to ceramide-induced cell death. It is important that inhibition of sphingosine kinases, during lipopolysaccharide stimulation, causes extensive ceramide accumulation and death of DCs. These data indicate that ceramide catabolism regulates survival of human DCs and reveal novel potential targets for the pharmacological manipulation of the immune response.
Franchi
Luigi
L
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
Malisan
Florence
F
Tomassini
Barbara
B
Testi
Roberto
R
D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002518:Ceramides / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005696:Galactosidases / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007110:Immunity, Active / Q000187:drug effects / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000276:immunology; D000099157:Sphingosine Kinase
D002518:Ceramides; D004791:Enzyme Inhibitors; D005696:Galactosidases; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase