In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice
In vivo over-expression of interleukin-10 increases resistance to focal brain ischemia in mice
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DOI：
10.1111/j.1471-4159.2009.06098.x
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发表时间：
2009-07-01
影响因子：
4.7
通讯作者：
Giannakopoulos, Panteleimon
中科院分区：
文献类型：
--
作者：
de Bilbao, Fabienne;Arsenijevic, Denis;Giannakopoulos, Panteleimon
早期研究表明，抗炎细胞因子白介素-10 （il -10）可预防小鼠永久性大脑中动脉闭塞（MCAO）。本研究利用主要组织相容性复合体Ea启动子介导的表达小鼠IL10 （IL10T）的转基因小鼠，探索慢性升高的IL10水平对mcao相关分子机制的影响。与野生型小鼠相比，IL10T的星形胶质细胞、小胶质细胞和内皮细胞中IL10过表达。MCAO 4天后，与野生型小鼠相比，IL10T小鼠的梗死面积减少了40%，这与活性caspase 3水平显著降低有关。基础条件下，IL10T动物脑内神经生长因子、谷胱甘肽等抗炎因子上调，促炎细胞因子IL1 β下调。此外，这些小鼠在小胶质细胞和内皮细胞中显示出基础谷胱甘肽水平的增加，以及内皮血管中锰超氧化物歧化酶的显著增加。缺血后，il - 10t小鼠的促炎细胞因子显著减少，包括肿瘤坏死因子- α、干扰素- γ和il - 1 β。我们的数据表明，组成性IL10过表达与脑缺血的显著抵抗有关，这可能归因于胶质/内皮细胞基础氧化还原特性的变化。
Early studies showed that the administration of the anti-inflammatory cytokine interleukin-10 (IL10) protects against permanent middle cerebral artery occlusion (MCAO) in mice. In this study, transgenic mice expressing murine IL10 (IL10T) directed by the major histocompatibility complex Ea promoter were produced and used to explore the effect of chronically increased IL10 levels on MCAO-related molecular mechanisms. IL10 was over-expressed in astrocytes, microglia, and endothelial brain cells in IL10T compared with wild type mice. Four days following MCAO, IL10T mice showed a 40% reduction in infarct size which was associated to significantly reduced levels of active caspase 3 compared with wild type mice. Under basal conditions, anti-inflammatory factors such as nerve growth factor and GSH were up-regulated and the pro-inflammatory cytokine IL1 beta was down-regulated in the brain of IL10T animals. In addition, these mice displayed increased basal GSH levels in microglial and endothelial cells as well as a marked increase in manganese superoxide dismutase in endothelial lining blood vessels. Following ischemia, IL10T mice showed a marked reduction in pro-inflammatory cytokines, including tumor necrosis factor-alpha, interferon-gamma, and IL1 beta. Our data indicate that constitutive IL10 over-expression is associated with a striking resistance to cerebral ischemia that may be attributed to changes in the basal redox properties of glial/endothelial cells.