Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta.
Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta.
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DOI：
10.4049/jimmunol.150.7.2659
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发表时间：
1993-04
影响因子：
4.4
通讯作者：
Sunhee C. Lee;Wei Liu;D. Dickson;C. Brosnan;J. Berman
中科院分区：
文献类型：
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作者：
Sunhee C. Lee;Wei Liu;D. Dickson;C. Brosnan;J. Berman
作为细胞因子在中枢神经系统发育和功能障碍中的作用研究的一部分，我们确定了从妊娠中期人类胎儿大脑中分离的高纯度小胶质细胞和星形胶质细胞培养物中细胞因子产生的模式。采用Northern blot和ELISA检测LPS、tnf - α或IL-1 β刺激前后tnf - α、IL-1 β和IL-6 mRNA和蛋白水平。在小胶质细胞中，LPS诱导了所有三种细胞因子的mRNA表达。培养基中也发现了高水平的IL-6和tnf - α蛋白，而IL-1 β蛋白主要与细胞相关。IL-1 β也诱导所有三种细胞因子的信息，按IL-1 β > IL-6 > tnf - α的顺序排列。tnf - α诱导IL-1 β mRNA和蛋白表达，但tnf - α和IL-6不表达。相比之下，LPS不能刺激星形胶质细胞中任何三种细胞因子的mRNA或蛋白表达。另一方面，IL-1 β对星形胶质细胞提供了强烈的刺激。IL-1 β诱导了tnf - α和IL-6的mRNA和蛋白，但两种细胞因子的反应动力学不同。tnf - α mRNA和蛋白质水平较早达到峰值（分别在4小时和16小时），72小时内检测不到，而IL-6 mRNA在较晚达到峰值（16小时），蛋白质水平在培养基中持续积累72小时。IL-1 β不诱导星形胶质细胞中IL-1 β mRNA或蛋白质。tnf - α不诱导星形胶质细胞中任何细胞因子的表达。总之，我们的研究结果表明，细胞因子的产生可以在人胎儿小胶质细胞和星形胶质细胞中诱导，但两种细胞类型的诱导刺激有显著差异。尽管LPS对小胶质细胞是一种强有力的刺激，但星形胶质细胞主要对IL-1 β有反应。这些数据进一步表明，小胶质细胞可能是星形胶质细胞反应的关键调节因子，主要通过细胞相关IL-1 β的表达起作用。
As part of a study on the role of cytokines in central nervous system development and dysfunction, we determined the pattern of cytokine production in highly purified cultures of microglia and astrocytes isolated from second-trimester human fetal brains. Levels of TNF-alpha, IL-1 beta, and IL-6 mRNA and protein were determined by Northern blot analysis and ELISA before and after stimulation with LPS, TNF-alpha, or IL-1 beta. In microglia, LPS induced mRNA for all three cytokines. High protein levels of IL-6 and TNF-alpha were also found in the medium, whereas IL-1 beta protein was mostly cell associated. IL-1 beta also induced message for all three cytokines, in the rank order of IL-1 beta > IL-6 > TNF-alpha. TNF-alpha induced mRNA and protein for IL-1 beta but not for TNF-alpha or IL-6. In contrast, LPS failed to stimulate either mRNA or protein expression for any of the three cytokines in astrocytes. On the other hand, IL-1 beta provided a strong stimulus for astrocytes. IL-1 beta induced mRNA and protein for both TNF-alpha and IL-6, but the kinetics of the response differed for the two cytokines. TNF-alpha mRNA and protein levels peaked early (at 4 h and 16 h, respectively) and were undetectable by 72 h, whereas IL-6 mRNA peaked later (at 16 h) and protein levels continued to accumulate in the medium through 72 h. IL-1 beta did not induce IL-1 beta mRNA or protein in astrocytes. TNF-alpha did not induce expression of any of the cytokines in astrocytes. In conclusion, our results demonstrate that cytokine production can be induced in human fetal microglia and astrocytes but that the stimuli for induction differed significantly for the two cell types. Whereas LPS was a potent stimulus for microglia, astrocytes primarily responded to IL-1 beta. The data further suggest that microglia may be key regulators of astrocyte response, working primarily through the expression of cell-associated IL-1 beta.