Nitta T, Sato K, Allegretta M, Brocke S, Lim M, Mitchell D J, Steinman L
Department of Neurology and Neurological Science, Stanford University School of Medicine, CA 94305-5235.
Brain Res. 1992 Jan 31;571(1):19-25. doi: 10.1016/0006-8993(92)90505-4.
Expression of granulocyte (G) and granulocyte-macrophage (GM) colony stimulating factor (CSF) genes in human cells of astroglial lineage was studied. Primers for CSFs were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and 8 fresh brain specimens by polymerase chain reaction. Constitutive expression of mRNA transcripts of GM-CSF could be detected in all astrocytoma and one neuroblastoma cell lines, and two out of 5 unstimulated astrocytomas, U87MG and U138 MG, expressed G-CSF genes. After stimulation with interleukin (IL)-1 beta + tumor necrosis factor (TNF)-alpha, all cell lines expressed G-CSF. In addition to the cultured cells, we examined gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The results show that some of the tumor and its surrounding reactive lesions express G- and GM-CSF genes but normal brains do not. The concentration of G- and GM-CSF in supernatants of cultured cells was assessed at the protein level by ELISA. A low level of GM-CSF activity was constitutively present in all astrocytomas. G-CSF was detected in unstimulated U87MG and U138MG and other cell lines could synthesize G-CSF after the stimulation of IL-1 beta and TNF-alpha at the level of mRNA. Furthermore, the concentration of CSFs increased markedly upon stimulation with IL-1 beta and/or TNF-alpha in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived CSFs may participate in local immune reactions accompanying infection, degeneration and malignancies in the brain.
研究了人星形胶质细胞谱系细胞中粒细胞（G）和粒细胞-巨噬细胞（GM）集落刺激因子（CSF）基因的表达。使用CSF的引物，通过聚合酶链反应分析5种培养的人星形细胞瘤细胞系和8个新鲜脑标本中的RNA转录本。在所有星形细胞瘤和一种神经母细胞瘤细胞系中均可检测到GM-CSF mRNA转录本的组成性表达，5个未刺激的星形细胞瘤中有2个，即U87MG和U138 MG，表达G-CSF基因。用白细胞介素（IL）-1β+肿瘤坏死因子（TNF）-α刺激后，所有细胞系均表达G-CSF。除了培养的细胞外，我们还检测了人恶性星形细胞瘤、肿瘤周围脑组织和尸检正常脑组织中的基因表达。结果表明，部分肿瘤及其周围的反应性病变表达G和GM-CSF基因，而正常脑组织不表达。通过ELISA在蛋白质水平评估培养细胞上清液中G和GM-CSF的浓度。所有星形细胞瘤中均组成性存在低水平的GM-CSF活性。在未刺激的U87MG和U138MG中检测到G-CSF，其他细胞系在IL-1β和TNF-α刺激后在mRNA水平可合成G-CSF。此外，IL-1β和/或TNF-α刺激后，CSF的浓度以时间和剂量依赖性方式显著增加。从这些结果推测，星形胶质细胞衍生的CSF可能参与脑内伴随感染、变性和恶性肿瘤的局部免疫反应。
