Relative contribution of different receptor subtypes in the response of neuroblastoma cells to tumor necrosis factor-alpha

The effect of tumor necrosis factor-alpha (TNF-alpha) on neuronal viability has been investigated in the SK-N-BE neuroblastoma cell line. These cells undergo differentiation upon chronic treatment with retinoic acid. Exposure of SK-N-BE cells to TNF-alpha produced a proliferative response in undiffe rentiated cells, whereas a reduced cell number was observed in retinoic aci d (RA)-differentiated cultures. This biphasic response may be related to th e different expression of TNF-alpha receptors (TNFRs); a significant increa se in the density of TNFR1 was in fact observed following RA-induced differ entiation. Under these conditions, a pronounced increase in the formation o f ceramide-1-phosphate (which was prevented by the selective inhibitor of p hosphatidylcholine-specific phospholipase C, D609) and an activation of cas pase-3 upon TNF-alpha challenge were evident. Selective blockade of each TN FR subtype allowed a more detailed analysis of the effect observed. Preincu bation with an anti-TNFR1 antibody prevented the cytotoxic effect of TNF-al pha in RA-differentiated SK-N-BE cells, whereas the anti-TNFR2 antibody blo cked the proliferative activity of the cytokine in undifferentiated culture s.