Differential effects of interleukin-1beta on neurotoxicity, cytokine induction and glial reaction in specific brain regions.
Differential effects of interleukin-1beta on neurotoxicity, cytokine induction and glial reaction in specific brain regions.
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发表时间：
2005
影响因子：
3.3
通讯作者：
A. Depino;C. Ferrari;María Clara Pott Godoy;Rodolfo Tarelli;F. Pitossi
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作者：
A. Depino;C. Ferrari;María Clara Pott Godoy;Rodolfo Tarelli;F. Pitossi
适当的炎症反应对维持组织稳态至关重要。脑实质的炎症反应不同于外周、脑室和脑膜的炎症反应。然而，尽管炎症成分与许多中枢神经系统疾病有关，但不同脑区实质炎症反应的差异尚未完全阐明。在这里，我们对常见的促炎刺激il -1 β对海马、黑质、纹状体和皮层的影响进行了系统的比较。在注射il -1 β 1和6天后，我们检测了注射区和邻近区域的各种反应，包括细胞因子mRNA诱导、胶质细胞激活、免疫细胞浸润和神经元完整性的变化。我们发现，在给药il -1 β后，tgf - β的mRNA以特定区域的方式上调。与它在外周的反应相反，il -1 α在被测的实质区域没有可检测到的诱导。此外，有时在远离注射部位的区域也观察到细胞因子的诱导作用。有趣的是，在海马齿状回观察到il -1 β介导的神经变性，而在其他测试区域则没有。IL-1 β注射介导的细胞募集主要由多形核细胞（PMN）组成，即使在远离注射部位的区域，也与IL-1betamRNA诱导相关。这些结果表明，不同的实质区域对il -1 β有不同的炎症反应和神经退行性变。综上所述，我们的研究结果提供了一个更精确的大脑区域炎症的图像，并为基于区域炎症差异的结果差异解释提供了基础。
An appropriate inflammatory response is crucial for the maintenance of tissue homeostasis. The inflammatory responses seen in the brain parenchyma differ from those elicited in the periphery, ventricles and meninges. However, although an inflammatory component has been associated with many CNS diseases, the differences among parenchymal inflammatory responses in different brain regions have not yet been fully elucidated. Here, we performed a systematic comparison of the effects of a common pro-inflammatory stimulus, IL-1beta, on the hippocampus, substantia nigra, striatum and cortex. We determined various responses, including cytokine mRNA induction, glial activation, immune cell infiltration and changes in neuronal integrity, in both injected and adjacent regions 1 and 6 days after the injection of IL-1beta. We found that the mRNA for TGF-beta was up-regulated in a region-specific manner after IL-1beta administration. Contrary to its response in the periphery, IL-1alpha showed no detectable induction in the tested parenchymal regions. In addition, cytokine induction was also sometimes observed in regions distant from the site of injection. Interestingly, IL-1beta-mediated neurodegeneration was observed in the dentate gyrus of the hippocampus, but not in the other tested regions. The cellular recruitment mediated by IL-1 beta injection consisted mainly of polymorphonuclear cells (PMN), which correlated with IL-1betamRNA induction even in regions far from the injection site. These results indicate that various parenchymal regions show different inflammatory responses and neurodegeneration in response to IL-1beta. Taken together, our results provide a more precise picture of regional inflammation in the brain and should provide a basis for differential interpretation of results based on regional inflammatory differences.