Thrombin induces release of proinflammatory chemokines interleukin-8 and interferon-γ-induced protein-10 from cultured human fetal astrocytes.
Thrombin induces release of proinflammatory chemokines interleukin-8 and interferon-γ-induced protein-10 from cultured human fetal astrocytes.
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DOI：
10.1097/wnr.0b013e32835c1de4
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发表时间：
2013-01-09
期刊：
影响因子：
1.7
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中科院分区：
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凝血酶是一种多功能丝氨酸蛋白酶，通过裂解蛋白酶激活受体（PAR1和PAR4）诱导神经细胞的多种反应。凝血酶/PAR信号与脑卒中和其他中枢神经系统病变后发生的神经炎症反应有关。神经炎症反应涉及星形胶质细胞，并导致这些细胞中诱导的促炎趋化因子包括白细胞介素-8 （IL-8或CXCL8）和干扰素- γ诱导蛋白-10 （IP-10或CXCL10）。星形胶质细胞已知表达PARs，但凝血酶对星形胶质细胞趋化因子分泌的影响尚不清楚。在这里，我们描述了凝血酶在原代人胎儿星形细胞中诱导增殖/代谢活性和趋化因子分泌的能力。凝血酶诱导剂量依赖性星形胶质细胞增殖以及IL-8和IP-10的释放，但不诱导白细胞介素-6或趋化因子调节和正常T细胞的表达和分泌（RANTES）。趋化因子反应被PAR1激活肽模拟，而不是PAR4激活肽。我们的数据表明星形细胞趋化因子释放是中枢神经系统暴露于凝血酶引发的神经炎症反应的一部分。
Thrombin is a multifunctional serine proteinase that induces a variety of responses from neural cells by cleavage of proteinase-activated receptors (PARs) including PAR1 and PAR4. Thrombin/PAR signaling has been implicated in the neuroinflammatory response that occurs in the brain following stroke and other CNS pathologies. The neuroinflammatory response involves astrocytes and results in induction of pro-inflammatory chemokines including interleukin-8 (IL-8 or CXCL8) and interferon-gamma-induced protein-10 (IP-10 or CXCL10) in these cells. Astroctyes are known to express PARs, however the effect of thrombin on astrocytic chemokine secretion is unknown. Here we characterize the ability of thrombin to induce proliferation/metabolic activity and chemokine secretion in primary human fetal astrocytes. Thrombin induced dose-dependent astrocyte proliferation as well as release of both IL-8 and IP-10, but not interleukin-6 or the chemokine regulated and normal T cell expressed and secreted (RANTES). The chemokine responses were mimicked by PAR1, but not PAR4, activating peptides. Our data indicate that astrocytic chemokine release is part of the neuroinflammatory response triggered by the exposure of the CNS to thrombin.