Chemokine-induced cell death in CCR5-expressing neuroblastoma cells.
CCR5 is expressed in neurons but its function in this cellular context is hitherto poorly understood. We have generated CCR5-expressing SH-SY5Y neuroblastoma cells. CCR5 ligands induced cell death in these cells, but not in control neuroblastoma cells or in CCR5-expressing fibroblasts. CCR5-dependent killing of neuroblastoma cells occurred through apoptosis, since it was accompanied by caspase-3 activation and could be prevented by a caspase-3 inhibitor. Finally, cell killing by activated microglia was more rapid and extensive in CCR5-expressing neuroblastoma cells than in control cells. In summary, CCR5 may act as a death receptor in cells of neuronal lineage and therefore be involved in inflammatory neurodegeneration.
Cartier
Laetitia
L
Biology of Ageing Laboratory, Department of Geriatrics, Geneva University Hospitals, 1225 Chêne-Bourg, Switzerland.
Dubois-Dauphin
Michel
M
Hartley
Oliver
O
Irminger-Finger
Irmgard
I
Krause
Karl-Heinz
KH
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology* / Q000633:toxicity*; D018920:Coculture Techniques; D004789:Enzyme Activation / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D008024:Ligands; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D041681:NIH 3T3 Cells; D009447:Neuroblastoma / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D009474:Neurons / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014162:Transfection
D019742:Chemokines, CC; D008024:Ligands; D019713:Receptors, CCR5; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases