Tumor Necrosis Factor‐α (TNF‐α), Interferon‐γ, and Interleukin‐6 but Not TNF‐β Induce Differentiation of Neuroblastoma Cells: The Role of Nitric Oxide
Tumor Necrosis Factor‐α (TNF‐α), Interferon‐γ, and Interleukin‐6 but Not TNF‐β Induce Differentiation of Neuroblastoma Cells: The Role of Nitric Oxide
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肿瘤坏死因子-α (TNF-α)、干扰素-γ 和白介素-6（而非 TNF-β）诱导神经母细胞瘤细胞分化：一氧化氮的作用
DOI：
10.1046/j.1471-4159.1994.62041330.x
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发表时间：
1994
影响因子：
4.7
通讯作者：
M. Fresno
中科院分区：
文献类型：
--
作者：
M. Muñoz;E. Cano;C. A. O'Donnell;J. Doyle;F. Liew;M. Fresno
摘要：肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-7）和白细胞介素-6（IL-6）（但不是TNF-β）可以剂量依赖性方式诱导神经母细胞瘤细胞系N103的体外分化。N103的分化伴随着细胞生长和神经突形成的停滞。TNF-α和IFN-γ诱导神经母细胞瘤细胞分化可被一氧化氮（NO）合酶抑制剂l-NG-单甲基精氨酸特异性抑制。相比之下，IL-6对N103细胞的分化不受l-NG-单甲基精氨酸的影响。这些结果表明，TNF-α和IFN-γ，而不是IL-6，通过NO诱导神经母细胞瘤细胞的分化。这一发现证实了TNF-α和IFN-γ诱导的N103细胞的培养上清液，而不是IL-6，含有高水平的NO2-，其产生被l-NG-monomethyarginine抑制。此外，N103细胞的分化可以通过向培养基中添加硝普钠（NO产生剂）以剂量依赖性方式直接诱导。因此，这些数据表明，NO可能是某些细胞因子如TNF-α和IFN-γ诱导神经元细胞分化的重要介质，并且除了巨噬细胞样脑细胞之外，神经元细胞也可以被免疫刺激诱导产生大量NO。
Abstract: Tumor necrosis factor‐a (TNF‐α), interferon‐γ (IFN‐7), and interleukin‐6 (IL‐6), but not TNF‐β, can induce the in vitro differentiation of the neuroblastoma cell line N103 in a dose‐dependent manner. Differentiation of N103 was accompanied by the arrest of cell growth and neurite formation. The induction of neuroblastoma cell differentiation by TNF‐α and IFN‐γ can be specifically inhibited by a nitric oxide (NO) synthase inhibitor, l‐NG‐monomethylarginine. In contrast, the differentiation of N103 cells by IL‐6 was not affected by l‐NG‐monomethylarginine. These results indicate that TNF‐α and IFN‐γ, but not IL‐6, induce the differentiation of neuroblastoma cells via NO. This is confirmed by the finding that the culture super‐ natants of N103 cells induced by TNF‐α and IFN‐γ, but not that by IL‐6, contained high levels of NO2−, the production of which was inhibited by l‐NG‐monomethylarginine. Furthermore, the differentiation of N103 cells can be induced directly in a dose‐dependent manner by the addition of nitroprusside, a generator of NO, into the culture medium. These data therefore indicate that NO may be an important mediator in the induction of neuronal cell differentiation by certain cytokines such as TNF‐α and IFN‐γ and that neuronal cells, in addition to the macrophagelike brain cells, can be induced by immunological stimuli to produce large quantities of NO.
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DOI：
10.1073/pnas.88.14.6368
发表时间：
1991-07-01
影响因子：
11.1
作者：
DAWSON, VL;DAWSON, TM;SNYDER, SH
通讯作者：
SNYDER, SH
影响因子：
4.4
作者：
K. Selmaj;M. Farooq;W. T. Norton;C. Raine;C. Brosnan
通讯作者：
K. Selmaj;M. Farooq;W. T. Norton;C. Raine;C. Brosnan
影响因子：
4.4
作者：
I. Chung;E. Benveniste
通讯作者：
I. Chung;E. Benveniste
影响因子：
56.9
作者：
GIULIAN, D;LACHMAN, LB
通讯作者：
LACHMAN, LB