Role of ERK map kinase and CRM1 in IL-1beta-stimulated release of HMGB1 from cortical astrocytes.
Role of ERK map kinase and CRM1 in IL-1beta-stimulated release of HMGB1 from cortical astrocytes.
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作者：
Hayakawa, Kazuhide;Arai, Ken;Lo, Eng H.
传统上认为反应性星形胶质细胞会阻碍中风后大脑的可塑性。然而，我们先前表明，反应性星形胶质细胞也可能有助于中风恢复，部分通过释放一种称为高迁移率族蛋白1（HMGB 1）的核蛋白。在这里，我们调查的机制，使刺激星形胶质细胞释放HMGB 1。将大鼠原代星形胶质细胞暴露于IL-1b 24小时引起剂量依赖性HMGB 1反应。细胞裂解物的免疫染色和蛋白质印迹显示HMGB 1的细胞内水平增加。Western印迹证实IL-1b诱导HMGB 1释放到星形胶质细胞条件培养基中。MAP激酶信号通路参与其中。IL-1b增加磷酸化ERK水平，MEK/ERK抑制剂U 0126降低刺激的星形胶质细胞中HMGB 1的上调。由于HMGB 1是一种核蛋白，因此核蛋白输出者染色体区域维持1（CRM 1）的作用被评估为连接MAP激酶信号传导与HMGB 1释放的候选机制。IL-1b增加CRM 1的表达与HMGB 1从细胞核易位到细胞质一致。用ERK抑制剂U 0126阻断IL-1b刺激的HMGB 1释放伴随着CRM 1的下调。我们的研究结果表明，IL-1b通过ERK MAP激酶和CRM 1信号刺激活化的星形胶质细胞释放HMGB 1。这些数据表明，一种新的途径，炎症细胞因子可能会提高反应性星形胶质细胞释放促恢复介质中风后的能力。
Reactive astrocytes are traditionally thought to impede brain plasticity after stroke. However, we previously showed that reactive astrocytes may also contribute to stroke recovery, partly via the release of a nuclear protein called high-mobility group box 1 (HMGB1). Here, we investigate the mechanisms that allow stimulated astrocytes to release HMGB1. Exposure of rat primary astrocytes to IL-1b for 24 hrs elicited a dose-dependent HMGB1 response. Immunostaining and western blots of cell lysates showed increased intracellular levels of HMGB1. Western blots confirmed that IL-1b induced a release of HMGB1 into astrocyte conditioned media. MAP kinase signaling was involved. Levels of phospho-ERK were increased by IL-1b, and the MEK/ERK inhibitor U0126 decreased HMGB1 upregulation in the stimulated astrocytes. Since HMGB1 is a nuclear protein, the role of the nuclear protein exporter, chromosome region maintenance 1 (CRM1), was assessed as a candidate mechanism for linking MAP kinase signaling to HMGB1 release. IL-1b increased CRM1 expression in concert with a translocation of HMGB1 from nucleus into cytoplasm. Blockade of IL-1b -stimulated HMGB1 release with the ERK inhibitor U0126 was accompanied by a downregulation of CRM1. Our findings reveal that IL-1b stimulates the release of HMGB1 from activated astrocytes via ERK MAP kinase and CRM1 signaling. These data suggest a novel pathway by which inflammatory cytokines may enhance the ability of reactive astrocytes to release pro-recovery mediators after stroke.
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影响因子：
5.3
作者：
Le Gallic, L;Virgilio, L;Mavrothalassitis, G
通讯作者：
Mavrothalassitis, G
影响因子：
8.3
作者：
Hayakawa, Kazuhide;Mishima, Kenichi;Fujiwara, Michihiro
通讯作者：
Fujiwara, Michihiro
影响因子：
5.3
作者：
Kim, Jung-Bin;Choi, Joon Sig;Lee, Ja-Kyeong
通讯作者：
Lee, Ja-Kyeong
影响因子：
4.8
作者：
Park, JS;Svetkauskaite, D;Abraham, E
通讯作者：
Abraham, E
影响因子：
64.5
作者：
Deng, YB;Ren, XY;Wu, XW
通讯作者：
Wu, XW