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

Abstract:

: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 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-alpha 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-alpha 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-alpha in RA-differentiated SK-N-BE cells, whereas the anti-TNFR2 antibody blocked the proliferative activity of the cytokine in undifferentiated cultures.

journal_name

J Neurochem

authors

Condorelli F,Sortino MA,Stella AM,Canonico PL

doi

10.1046/j.1471-4159.2000.0751172.x

keywords:

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

1172-9

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

75

pub_type

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