Interleukin-1-beta and tumor necrosis factor-alpha increase peripheral-type benzodiazepine binding sites in cultured polygonal astrocytes.
Interleukin-1-beta and tumor necrosis factor-alpha increase peripheral-type benzodiazepine binding sites in cultured polygonal astrocytes.
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发表时间：
1992
影响因子：
4.7
通讯作者：
Y. J. Oh;J. Francis;G. Markelonis;T. Oh
中科院分区：
文献类型：
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作者：
Y. J. Oh;J. Francis;G. Markelonis;T. Oh
外周型苯二氮卓类结合位点（PTBBS）在受损的CNS中显著增加。星形胶质细胞似乎是表达增加的PTBBS的主要细胞类型。由于受损CNS内的某些细胞因子是星形胶质细胞的有效促有丝分裂剂，因此我们使用[3 H]Ro 5-4864作为特异性配体检测了两种此类细胞因子白细胞介素（IL）-1 β和肿瘤坏死因子（TNF）对培养星形胶质细胞中PTBBS的影响。纯化培养的多边形或过程轴承星形胶质细胞制备从新生大鼠大脑半球。在1.8 nM的浓度下，放射性配体与多边形星形胶质细胞的特异性结合在60分钟内达到平衡，并在5-10分钟达到半最大值。相比之下，与过程承载星形胶质细胞的特异性结合几乎没有超过背景水平。IL-1和TNF以剂量和时间依赖性方式增加多角形星形胶质细胞内的PTBBS。在10-50 ng/ml时，IL-1 β和TNF-α使多边形星形胶质细胞培养物中的[3 H]Ro 5-4864结合分别比对照培养物中的水平高65%和87%。然而，在多角形星形胶质细胞中，在IL-2处理后没有看到PTBBS的变化。饱和结合实验的Scatchard分析表明，由TNF促进的PTBBS的增加是由于多边形星形胶质细胞中存在的结合位点的数量增加，而不是由于受体亲和力的增加。结合数据表明，PTBBS内的过程轴承星形胶质细胞的文化几乎不存在，无论治疗。这些体外数据表明，在受伤的大脑中发现的某些细胞因子可能参与上调PTBBS内的一个特定亚型的星形胶质细胞。
Peripheral-type benzodiazepine binding sites (PTBBS) are markedly increased in the injured CNS. Astrocytes appear to be the primary cell type which express increased PTBBS. Because certain cytokines within the injured CNS are potent mitogens for astrocytes, we examined the effects of two such cytokines, interleukin (IL)-1 beta and tumor necrosis factor (TNF), on PTBBS in cultured astrocytes using [3H]Ro 5-4864 as the specific ligand. Purified cultures of either polygonal or process-bearing astrocytes were prepared from neonatal rat cerebral hemispheres. At a concentration of 1.8 nM, specific binding of the radioactive ligand to polygonal astrocytes reached equilibrium within 60 min and was half-maximal by 5-10 min. By contrast, specific binding to process-bearing astrocytes barely exceeded background levels. IL-1 and TNF increased PTBBS within polygonal astrocytes in both dose- and time-dependent manners. At 10-50 ng/ml, IL-1 beta and TNF-alpha elevated [3H]Ro 5-4864 binding in polygonal astrocyte cultures 65 and 87%, respectively, above the level in control cultures. However, no changes in PTBBS were seen within polygonal astrocytes after IL-2 treatment. Scatchard analysis of saturation binding experiments suggested that the increase in PTBBS promoted by TNF was due to an increased number of binding sites present in polygonal astrocytes and not due to an increase in receptor affinity. Binding data suggested that PTBBS within cultures of process-bearing astrocytes were virtually absent irrespective of the treatment. These in vitro data suggest that certain cytokines found in the injured brain may be involved in up-regulating PTBBS within a particular subtype of astrocyte.