Lichtenstein Mathieu P, Madrigal José L M, Pujol Aurora, Galea Elena
Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
Neurosignals. 2012;20(2):86-102. doi: 10.1159/000330805. Epub 2011 Dec 22.
While the role of cytokines in causing pro- and anti-inflammatory cascades in the brain and that of chemokines in promoting chemotaxis is well recognized, the immunomodulatory actions of neurotrophins released during brain injury remains largely undetermined. This knowledge gap affects basic fibroblast growth factor (FGF2), which in the brain is mainly produced by astrocytes and characteristically upregulated in reactive astrocytes. The goal of this study was to characterize the inflammatory actions of FGF2 in astrocytes using primary cultures. We report that FGF2 induced the upregulation of monocyte chemoattractant protein (CCL2) and cyclo-oxygenase type 2 (COX2), and the inhibition of lipopolysaccharide-elicited ICAM1 upregulation. The effects of FGF2 were: (i) dependent on gene transcription as revealed by the concomitant regulation of CCL2 or ICAM1 mRNAs; (ii) mediated by the FGF2 receptor type 2; (iii) dependent on ERK, JNK and FAK, and (iv) NF-κB-independent. FGF2 also caused accelerated wound closure dependent on CCL2, COX2, ERK, JNK and FAK in a scratch assay. We conclude that the signaling network triggered by FGF2 in astrocytes converged into accelerating directed motion. It follows that astrocyte migration to injury sites may be a key factor in the repair mechanisms orchestrated by FGF2.
虽然细胞因子在引发大脑中的促炎和抗炎级联反应中的作用以及趋化因子在促进趋化作用中的作用已得到充分认识，但脑损伤期间释放的神经营养因子的免疫调节作用在很大程度上仍未确定。这一知识空白影响到碱性成纤维细胞生长因子（FGF2），在大脑中它主要由星形胶质细胞产生，并在反应性星形胶质细胞中典型地上调。本研究的目的是使用原代培养来表征FGF2在星形胶质细胞中的炎症作用。我们报告FGF2诱导单核细胞趋化蛋白（CCL2）和环氧化酶2型（COX2）上调，并抑制脂多糖诱导的ICAM1上调。FGF2的作用为：（i）如CCL2或ICAM1 mRNA的伴随调节所揭示的那样，依赖于基因转录；（ii）由2型FGF2受体介导；（iii）依赖于ERK、JNK和FAK，以及（iv）不依赖于NF-κB。在划痕试验中，FGF2还导致依赖于CCL2、COX2、ERK、JNK和FAK的伤口愈合加速。我们得出结论，FGF2在星形胶质细胞中触发的信号网络汇聚成加速定向运动。因此，星形胶质细胞向损伤部位的迁移可能是FGF2精心策划的修复机制中的一个关键因素。
