Chen Shuzhen, Luo Defang, Streit Wolfgang J, Harrison Jeffrey K
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610-0267, USA.
J Neuroimmunol. 2002 Dec;133(1-2):46-55. doi: 10.1016/s0165-5728(02)00354-5.
Following peripheral nerve transection, CX3CR1 and TGF-beta1 are increased in a time-dependent manner within the injured facial motor nucleus. To explore the relationship between TGF-beta1 and CX3CR1 in the CNS, the effects of TGF-beta1 on CX3CR1 mRNA, protein and fractalkine-dependent stimulation of signal transduction cascades in primary cultures of rat microglia were examined. TGF-beta1 increased steady state levels of CX3CR1 mRNA, 125I-fractalkine binding sites and blunted fractalkine-stimulated ERK1/2 phosphorylation. The half-life of CX3CR1 mRNA was unaltered by TGF-beta1 and two potential Smad binding elements (SBEs) were identified in the rat CX3CR1 promoter. TGF-beta1 may shift fractalkine-dependent signaling away from activation of ERK1/2 towards other pathways and/or may provide a mechanism for microglia to more strongly adhere to neurons.
外周神经横断后，CX3CR1和转化生长因子β1（TGF-β1）在受损的面神经运动核内呈时间依赖性增加。为了探究中枢神经系统中TGF-β1与CX3CR1之间的关系，研究了TGF-β1对大鼠小胶质细胞原代培养物中CX3CR1 mRNA、蛋白以及趋化因子依赖性信号转导级联反应刺激的影响。TGF-β1增加了CX3CR1 mRNA的稳态水平、125I-趋化因子结合位点，并减弱了趋化因子刺激的细胞外信号调节激酶1/2（ERK1/2）磷酸化。TGF-β1未改变CX3CR1 mRNA的半衰期，并且在大鼠CX3CR1启动子中鉴定出两个潜在的Smad结合元件（SBEs）。TGF-β1可能会使趋化因子依赖性信号从ERK1/2的激活转向其他途径，和/或可能为小胶质细胞更强烈地黏附于神经元提供一种机制。
