Selective proinflammatory activation of astrocytes by high-mobility group box 1 protein signaling
Selective proinflammatory activation of astrocytes by high-mobility group box 1 protein signaling
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DOI：
10.4049/jimmunol.179.12.8525
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发表时间：
2007-12-15
影响因子：
4.4
通讯作者：
Melloni, Edon
中科院分区：
文献类型：
--
作者：
Pedrazzi, Marco;Patrone, Mauro;Melloni, Edon
细胞外高迁移率组框1蛋白（HMGB1）触发大脑炎症事件。我们证明星形胶质细胞，大脑中的主要胶质细胞，在暴露于HMGB1时获得特定的反应表型。这种细胞活化涉及晚期糖基化终产物受体和MAPK/ERK1/2级联，导致转录/翻译诱导有限数量的炎症介质，包括环氧化酶-2、基质金属蛋白酶-9和CC和CXC家族的几种趋化因子。hmgb1反应星形胶质细胞释放的混合因子对人单核细胞具有强效的趋化活性。本研究首次提出HMGB1/星形胶质细胞相互作用通过促进局部白细胞浸润在中枢神经系统炎症过程的进展中发挥特定的功能作用。
Extracellular high-mobility group box 1 protein (HMGB1) triggers inflammatory events in the brain. We demonstrate that astrocytes, the main glial cells in the brain, acquire a specific reactive phenotype when exposed to HMGB1. This cell activation, which involves the receptor for advanced glycation end-products and the MAPK/ERK1/2 cascade, results in the transcriptional/ translational induction of a restricted number of inflammatory mediators, including cyclooxygenase-2, matrix metalloproteinase-9, and several chemokines of the CC and CXC families. The mixture of factors released by HMGB1-reactive astrocytes displays a potent chemotactic activity on human monocytic cells. This study is the first to suggest that HMGB1/astrocyte interaction plays a specific functional role in the progression of inflammatory processes in the CNS by facilitating local leukocyte infiltration.