Condorelli F, Sortino M A, Stella A M, Canonico P L
Institute of Pharmacology, University of Catania, Italy.
J Neurochem. 2000 Sep;75(3):1172-9. doi: 10.1046/j.1471-4159.2000.0751172.x.
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.
已在SK-N-BE神经母细胞瘤细胞系中研究了肿瘤坏死因子-α（TNF-α）对神经元活力的影响。这些细胞在长期用视黄酸处理后会发生分化。将SK-N-BE细胞暴露于TNF-α会在未分化细胞中产生增殖反应，而在视黄酸（RA）分化的培养物中观察到细胞数量减少。这种双相反应可能与TNF-α受体（TNFRs）的不同表达有关；事实上，在RA诱导分化后，TNFR1的密度显著增加。在这些条件下，明显观察到神经酰胺-1-磷酸的形成显著增加（这被磷脂酰胆碱特异性磷脂酶C的选择性抑制剂D609所阻止），并且在TNF-α刺激后caspase-3被激活。对每种TNFR亚型的选择性阻断使得能够更详细地分析所观察到的效应。用抗TNFR1抗体预孵育可防止TNF-α对RA分化的SK-N-BE细胞产生细胞毒性作用，而抗TNFR2抗体则阻断了细胞因子在未分化培养物中的增殖活性。
