Interleukin-1β induces apoptosis in GL15 glioblastoma-derived human cell line
Interleukin-1β induces apoptosis in GL15 glioblastoma-derived human cell line
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DOI：
10.1152/ajpcell.2000.279.6.c2043
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发表时间：
2000-12-01
影响因子：
5.5
通讯作者：
Bocchini, V
中科院分区：
文献类型：
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作者：
Castigli, E;Arcuri, C;Bocchini, V
白细胞介素1-β（IL-1 β）诱导胶质母细胞瘤衍生的人细胞系凋亡，表现出低分化星形胶质细胞表型。通过分析细胞核形态、原位DNA片段化和细胞质核小体的ELISA检测证实了凋亡作用。我们将GL15细胞的分化程度与凋亡反应相关联：1）4 '，6-二脒基-2-苯基吲哚染色，结合胶质细胞酸性蛋白（GFAP）免疫荧光，显示具有凋亡核的细胞表达低水平的GFAP;和2）在传代培养13天时，在更分化的状态下，GL15细胞对IL-1 β没有凋亡反应。在这个细胞系中，非随机的染色体变化和SV40早期区域的表达已经被证明。假设p42/p44丝裂原活化蛋白激酶（MAPK）通路参与IL-1 β诱导的细胞凋亡。已有研究表明，SV40小T抗原部分抑制磷酸酶2A，导致p42/p44 MAPK通路的稳态活性增强。PD-098059是p42/p44 MAPK通路的特异性抑制剂，可抵消IL-1 β的凋亡作用，而SB-203580是p38应激活化蛋白激酶（SAPK）通路的特异性抑制剂，则无效。MAPK和SAPK途径之间的不平衡已被认为是决定细胞命运的关键因素。我们的研究结果表明，进一步刺激p42/p44 MAPK通路可以构成肿瘤细胞的死亡信号，其中基因组损伤和MAPK通路控制的改变发生。
Interleukin 1-beta (IL-1 beta) induces apoptosis in a glioblastoma-derived human cell line, exhibiting a poorly differentiated astrocytic phenotype. The apoptotic effect was demonstrated by analyzing nuclear morphology, in situ DNA fragmentation, and by ELISA detection of cytoplasmatic nucleosomes. We correlated the degree of differentiation of GL15 cells with the apoptotic response: 1) 4', 6-diamidino-2-phenylindole staining, combined with glial fibrillary acidic protein (GFAP) immunofluorescence, showed that the cells with apoptotic nuclei express low levels of GFAP; and 2) at 13 days of subculture, in a more differentiated state, GL15 cells did not respond with apoptosis to IL-1 betab. In this cell line, nonrandom chromosome changes and the expression of SV40 early region have been previously shown. The involvement of p42/p44 mitogen-activated protein kinase (MAPK) pathway in the induction of apoptosis by IL-1 beta was hypothesized. Previous studies have shown that SV40 small T antigen partially inhibits phosphatase 2A, leading to an enhancement of the steady-state activity of p42/p44 MAPK pathway. PD-098059, specific inhibitor of p42/p44 MAPK pathway, counteracts the apoptotic effect of IL-1 beta, whereas SB-203580, specific inhibitor of p38 stress-activated protein kinase (SAPK) pathway, is ineffective. The imbalance between MAPK and SAPK pathways has been proposed as a key factor in determination of cell fate. Our results demonstrate that a further stimulation of p42/p44 MAPK pathway can constitute a death signal in tumor cells in which genomic damage and MAPK pathway control alterations occur.