INTERLEUKIN-6 AND TRANSFORMING GROWTH-FACTOR-BETA-1 MESSENGER-RNAS ARE INDUCED IN RAT FACIAL NUCLEUS FOLLOWING MOTONEURON AXOTOMY
INTERLEUKIN-6 AND TRANSFORMING GROWTH-FACTOR-BETA-1 MESSENGER-RNAS ARE INDUCED IN RAT FACIAL NUCLEUS FOLLOWING MOTONEURON AXOTOMY
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DOI：
10.1111/j.1460-9568.1993.tb00929.x
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发表时间：
1993-07-01
影响因子：
3.4
通讯作者：
KREUTZBERG, GW
中科院分区：
文献类型：
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作者：
KIEFER, R;LINDHOLM, D;KREUTZBERG, GW
大鼠面神经横断导致轴突切断运动神经元周围星形胶质细胞和小胶质细胞的快速激活。参与体内胶质细胞活化的因素定义不清，但细胞因子已被认为是体外胶质细胞活性的主要调节因子。在本研究中，我们研究了细胞因子mRNA的表达在轴突切断面神经核，可能参与胶质细胞活化。面神经切断后8小时，已诱导白细胞介素（IL）-6-mRNA的快速积累，在24小时达到高峰。未手术对照侧未检测到IL-6 mRNA。在正常面神经核中检测到低水平的转化生长因子（TGF）-β 1 mRNA，轴突切断后2天增加到正常水平的3倍。第7天后，TGF-β 1 mRNA水平逐渐下降，第二个小高峰后21天轴突切断。原位杂交实验，4和21天后，轴突切断，本地化TGF-β 1 mRNA的再生运动神经元周围的激活的小胶质细胞，以及可能一些星形胶质细胞。运动神经元不表达TGF-β 1 mRNA。TGF-β 3在面神经核中正常表达，但不受轴突切断的调节。在任何时间点，在再生的面神经核中均未发现IL-1、肿瘤坏死因子-α或干扰素-γ的mRNA。我们的数据表明，IL-6可能作为一个早期激活信号的神经胶质细胞在响应运动神经元轴突切断，和TGF-β 1表达的激活的神经胶质细胞可能提供一个持久的负反馈信号，以控制胶质细胞的激活。
Transection of the rat facial nerve leads to a rapid activation of both astrocytes and microglia around axotomized motoneurons. The factors involved in glial activation in vivo are poorly defined but cytokines have been implicated as major regulators of glial activity in vitro. In the present study we have investigated the expression of cytokine mRNAs in the axotomized facial nucleus that might be involved in glial activation. Eight hours after axotomy unilateral transection of the facial nerve had already induced a rapid accumulation of interleukin (IL)-6-mRNA, with a peak at 24 hours. No IL-6 mRNA was detected on the unoperated control side. Transforming growth factor (TGF)-beta1 mRNA was detected at low levels in the normal facial nucleus, increasing to three times the normal level 2 days after axotomy. After day 7 TGF-beta1 mRNA levels gradually declined, with a second minor peak 21 days after axotomy. In situ hybridization experiments, 4 and 21 days after axotomy, localized TGF-beta1 mRNA to activated microglial cells around regenerating motoneurons, as well as probably some astrocytes. Motoneurons did not express TGF-beta1 mRNA. TGF-beta3 was found to be normally expressed in the facial nucleus but was not regulated by axotomy. No mRNA for IL-1, tumour necrosis factor-alpha or interferon-gamma was found in the regenerating facial nucleus at any point in time. Our data indicate that IL-6 might act as an early activating signal for glial cells in response to motoneuron axotomy, and that TGF-beta1 expressed by activated glial cells might provide a long-lasting negative feedback signal to control glial activation.