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Relative Contribution of Different Receptor Subtypes in the Response of Neuroblastoma Cells to Tumor Necrosis Factor‐α
Author(s) -
Condorelli Fabrizio,
Sortino Maria Angela,
Stella Anna Maria Giuffrida,
Caico Pier Luigi
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751172.x
Subject(s) - retinoic acid , tumor necrosis factor alpha , cytotoxic t cell , cytokine , neuroblastoma , receptor , cell culture , biology , endocrinology , antibody , microbiology and biotechnology , nerve growth factor , medicine , chemistry , cancer research , immunology , biochemistry , in vitro , genetics
The effect of tumor necrosis factor‐α (TNF‐α) 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‐α produced a proliferative response in undifferentiated cells, whereas a reduced cell number was observed in retinoic acid (RA)‐differentiated cultures. This biphasic response may be related to the different expression of TNF‐α receptors (TNFRs); a significant increase in the density of TNFR1 was in fact observed following RA‐induced differentiation. Under these conditions, a pronounced increase in the formation of ceramide‐1‐phosphate (which was prevented by the selective inhibitor of phosphatidylcholine‐specific phospholipase C, D609) and an activation of caspase‐3 upon TNF‐α challenge were evident. Selective blockade of each TNFR subtype allowed a more detailed analysis of the effect observed. Preincubation with an anti‐TNFR1 antibody prevented the cytotoxic effect of TNF‐α in RA‐differentiated SK‐N‐BE cells, whereas the anti‐TNFR2 antibody blocked the proliferative activity of the cytokine in undifferentiated cultures.