Tilleux Sébastien, Berger Julie, Hermans Emmanuel
Laboratoire de Pharmacologie Expérimentale, Université catholique de Louvain, 54.10, Av. Hippocrate 54, 1200 Brussels, Belgium.
J Neuroimmunol. 2007 Sep;189(1-2):23-30. doi: 10.1016/j.jneuroim.2007.06.011. Epub 2007 Jul 12.
To explore the impact of neuroinflammation on the control of glutamate transmission, we studied the metabotropic glutamate receptor 5 (mGluR5) expression in cultured astrocytes exposed to conditioned medium from lipopolysaccharide-activated microglia. This treatment caused profound changes in astrocyte phenotype that correlated with altered expression of GFAP and vimentin. This putative astrogliosis was accompanied by a down-regulation of mGluR5 protein and mRNA expression, with a maximal effect after 48 h treatment (up to 50% decrease). Such regulation was not observed with medium from naive microglia but was mimicked by direct addition of tumor necrosis factor, a major cytokine released from activated microglia. Conversely, treatment with prostaglandin E2 and induction of nitric oxide production resulted in a significant up-regulation of mGluR5. These results suggest that complex crosstalks between microglia and astrocytes during neuroinflammatory insults would influence glutamate-dependent responses in astrocytes.
为了探究神经炎症对谷氨酸传递控制的影响，我们研究了暴露于脂多糖激活的小胶质细胞条件培养基中的培养星形胶质细胞中代谢型谷氨酸受体5（mGluR5）的表达。这种处理导致星形胶质细胞表型发生深刻变化，这与胶质纤维酸性蛋白（GFAP）和波形蛋白表达的改变相关。这种假定的星形胶质细胞增生伴随着mGluR5蛋白和mRNA表达的下调，在处理48小时后效果最为显著（最多降低50%）。未活化小胶质细胞的培养基未观察到这种调节作用，但直接添加肿瘤坏死因子（一种从活化小胶质细胞释放的主要细胞因子）可模拟这种调节作用。相反，用前列腺素E2处理并诱导一氧化氮产生会导致mGluR5显著上调。这些结果表明，在神经炎症损伤期间，小胶质细胞和星形胶质细胞之间复杂的相互作用会影响星形胶质细胞中谷氨酸依赖性反应。
