Intercellular adhesion molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6.
Intercellular adhesion molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6.
复制标题
DOI：
10.4049/jimmunol.155.3.1489
复制
发表时间：
1995-08
影响因子：
4.4
通讯作者：
P. Shrikant;E. Weber;Tamas Jilling;E. Benveniste
中科院分区：
文献类型：
--
作者：
P. Shrikant;E. Weber;Tamas Jilling;E. Benveniste
中枢神经系统包含两种主要的胶质细胞类型，星形胶质细胞和小胶质细胞，它们在中枢神经系统中起免疫效应细胞的作用。我们一直在研究神经胶质细胞表达参与免疫反应的基因产物的能力，重点是ICAM-1的表达。我们之前证明了三种促炎细胞因子，tnf - α， IL-1 β和ifn - γ，以及ifn - γ加LPS，可以增强大鼠星形胶质细胞中ICAM-1的表达。在本研究中，我们检测了ICAM-1在原代大鼠小胶质细胞中的表达，发现只有ifn - γ和ifn - γ /LPS能增强ICAM-1基因的表达。这些数据表明，星形胶质细胞和小胶质细胞的ICAM-1表达受到各种促炎细胞因子的不同增强。接下来，我们检测了两种细胞因子IL-10和IL-6对ICAM-1表达的影响。单独IL-10对ICAM-1表达没有影响，但在两种细胞类型中，IL-10抑制ICAM-1胞内和膜蛋白表达的增强，尽管它对ICAM-1稳态mRNA水平没有影响。这些结果表明IL-10在翻译和/或翻译后水平上影响ICAM-1的表达。单独IL-6对星形胶质细胞和小胶质细胞中ICAM-1的表达也没有影响，但IL-6抑制了这些细胞中ICAM-1 mRNA和蛋白的表达。IL-6对ICAM-1 mRNA稳态水平的抑制不是ICAM-1信息降解的结果，这表明在转录水平上有影响。因此，IL-10和IL-6都可以抑制胶质细胞的ICAM-1表达，尽管它们的作用机制不同。
The central nervous system contains two major glial cell types, astrocytes and microglia, which function as immune effector cells within the central nervous system. We have been studying the ability of glial cells to express gene products involved in immune responsiveness, with an emphasis on expression of ICAM-1. We demonstrated previously that three proinflammatory cytokines, TNF-alpha, IL-1 beta, and IFN-gamma, as well as IFN-gamma plus LPS, can enhance ICAM-1 expression by primary rat astrocytes. In this study, we examined ICAM-1 expression by primary rat microglia and found that only IFN-gamma and IFN-gamma/LPS enhance ICAM-1 gene expression. These data indicate that ICAM-1 expression by astrocytes and microglia is enhanced differentially by various proinflammatory cytokines. We next examined the effect of two cytokines, IL-10 and IL-6, on ICAM-1 expression. IL-10 alone has no effect on ICAM-1 expression, but it inhibits the enhancement of ICAM-1 intracellular and membrane protein expression in both cell types, although it has no influence on ICAM-1 steady-state mRNA levels. These results suggest that IL-10 affects ICAM-1 expression at the translational and/or post-translational level. IL-6 alone also had no effect on ICAM-1 expression in either astrocytes or microglia, but it inhibited induction of both ICAM-1 mRNA and protein expression in these cells. Inhibition of ICAM-1 mRNA steady-state levels by IL-6 was not the result of degradation of the ICAM-1 message, suggesting an effect at the transcriptional level. Thus, both IL-10 and IL-6 can inhibit ICAM-1 expression by glial cells, although they do so by contrasting mechanisms.