CONSTITUTIVE AND CYTOKINE-REGULATED EXPRESSION OF PRESENILIN-1 AND PRESENILIN-2 GENES IN HUMAN NEURAL CELL LINES

为了研究多效性神经元和胶质细胞因子在人神经细胞中早老素（PS）基因表达调控中的作用，采用Northern blotting分析了SK-N-SH神经母细胞瘤、IMR-32神经母细胞瘤、NTera2畸胎癌衍生分化神经元（NTera2- n）和U-373MG星形细胞瘤细胞暴露于促炎细胞因子（TNF-α、IFN-γ或IL-1β）后的早老素-1 （PS1）和早老素-2 (PS2) mRNA水平。抗炎细胞因子（IL-10或TGF-β1），二丁基环AMP或phorbol 12-肉豆蔻酸13-乙酸酯（PMA）。PS1 （3.0 kb）和PS2 (2.3 kb) mRNA的组成表达在所有这些细胞系中都被鉴定出来，其中PS1 mRNA的水平在任何细胞因子和因子处理后都没有改变。相比之下，SK-N-SH细胞暴露于TNF-α和U-373MG细胞暴露于IFN-γ后PS2 mRNA表达显著上调，而NTera2-N和U-373MG细胞暴露于il -1β或PMA后PS2 mRNA表达均下调。经过这些处理后，IMR-32细胞中的PS2 mRNA水平保持不变。这些结果表明，PS1和PS2基因在一组人类神经细胞系中组成性地表达，其中PS2 mRNA的表达受到一组不同细胞因子的影响，这些细胞因子通过细胞类型特异性机制不改变PS1 mRNA水平，这表明在人类神经细胞中存在控制PS1和PS2基因表达的分离调控系统。

To investigate the role of pleiotropic neuronal and glial cytokines in the regulation of presenilin (PS) gene expression in human neural cells, both presenilin-1 (PS1) and presenilin-2 (PS2) mRNA levels were analyzed by Northern blotting in SK-N-SH neuroblastoma, IMR-32 neuroblastoma, NTera2 teratocarcinoma-derived differentiated neurons (NTera2-N), and U-373MG astrocytoma cells following exposure to proinflammatory cytokines (TNF-α, IFN-γ, or IL-1β), anti -inflammatory cytokines (IL-10 or TGF-β1), dibutyryl cyclic AMP or phorbol 12-myristate 13-acetate (PMA). The constitutive expression of PS1 (3.0 kb) and PS2 (2.3 kb) mRNA was identified in all these cell lines, in which PS1 mRNA levels were unaltered following treatment with any cytokines and factors examined. By contrast, PS2 mRNA expression was up-regulated substantially in SK-N-SH cells by exposure to TNF-α and in U-373MG cells by treatment with IFN-γ, whereas it was down-regulated in both NTera2-N and U-373MG cells following exposure to IL-1βor PMA. The levels of PS2 mRNA remained unchanged in IMR-32 cells after these treatment. These results indicate that PS1 and PS2 genes are expressed constitutively in a panel of human neural cell lines where PS2 mRNA expression is affected by a distinct set of cytokines via cell type-specific mechanisms that do not alter PS1 mRNA levels, suggesting the existence of separated regulatory systems controlling the expression of PS1 and PS2 genes in human neural cells.