Interleukin-1β and anaphylatoxins exert a synergistic effect on NGF expression by astrocytes
Interleukin-1β and anaphylatoxins exert a synergistic effect on NGF expression by astrocytes
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DOI：
10.1186/1742-2094-3-8
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发表时间：
2006-04-04
影响因子：
9.3
通讯作者：
Fontaine, Marc
中科院分区：
文献类型：
--
作者：
Jauneau, Anne-christine;Ischenko, Alexander;Fontaine, Marc
C3a和C5a过敏毒素是补体激活过程中释放的促炎多肽。它们通过分别与两种G蛋白偶联受体C3aR和C5aR相互作用发挥生物活性。在大脑中，这些受体在神经胶质细胞上表达，最近的一些数据表明过敏毒素可以介导神经保护。本研究采用RT-PCR和核糖核酸酶保护实验（RPA）研究了过敏毒素对人胶质母细胞瘤细胞株T98G和大鼠星形胶质细胞神经营养因子表达的影响。我们的数据表明，对于两种细胞类型，过敏毒素上调NGF mRNA的表达。这种反应依赖于G蛋白偶联途径，因为百日咳毒素（PTX）预处理的细胞完全阻断了NGF mRNA的增加。这种作用是过敏毒素特异性的，因为预先用抗C3a或抗c5ar抗体孵育分别消除了C3a和C5a的作用。过敏毒素对NGF mRNA的调节不伴有翻译成蛋白的表达，但过敏毒素/IL-1b共刺激存在显著的协同效应。我们证明了过敏毒素参与星形胶质细胞释放NGF的过程，这表明C3a和C5a可以调节中枢神经系统中的神经元存活。
C3a and C5a anaphylatoxins are proinflammatory polypeptides released during complement activation. They exert their biological activities through interaction with two G protein-coupled receptors named C3aR and C5aR, respectively. In the brain, these receptors are expressed on glial cells, and some recent data have suggested that anaphylatoxins could mediate neuroprotection. In this study, we used RT-PCR and ribonuclease protection assays (RPA) to investigate the role of anaphylatoxins on neurotrophin expression by the human glioblastoma cell line T98G and by rat astrocytes. Our data show that for both cell types, anaphylatoxins upregulate expression of NGF mRNA. This response depended on a G protein-coupled pathway since pre-treatment of cells with pertussis toxin (PTX) completely blocked NGF mRNA increases. This effect was anaphylatoxin-specific since pre-incubation with anti-C3a or anti-C5aR antibodies abolished the effects of C3a and C5a, respectively. The regulation of NGF mRNA by anaphylatoxins was not accompanied by translation into protein expression, but there was a significant synergic effect of anaphylatoxins/IL-1b costimulation. Our demonstration of involvement of anaphylatoxins in the NGF release process by astrocytes suggests that C3a and C5a could modulate neuronal survival in the CNS.