Simmons Sarah, Lee Richard V, Möller Thomas, Weinstein Jonathan R
Department of Neurology, School of Medicine, University of Washington, Seattle, Washington 98195, USA.
Neuroreport. 2013 Jan 9;24(1):36-40. doi: 10.1097/WNR.0b013e32835c1de4.
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 central nervous system pathologies. The neuroinflammatory response involves astrocytes and results in induction of proinflammatory chemokines including interleukin-8 (IL-8 or CXCL8) and interferon-γ-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 induces dose-dependent astrocyte proliferation as well as release of both IL-8 and IP-10, but not IL-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 central nervous system to thrombin.
凝血酶是一种多功能丝氨酸蛋白酶，它通过切割蛋白酶激活受体（PARs），包括PAR1和PAR4，诱导神经细胞产生多种反应。凝血酶/PAR信号传导与中风和其他中枢神经系统疾病后大脑中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，并导致这些细胞中促炎趋化因子的诱导，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）。已知星形胶质细胞表达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胶质细胞中诱导增殖/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IL-6或趋化因子调节的正常T细胞表达和分泌（RANTES）。PAR1激活肽可模拟趋化因子反应，但PAR4激活肽不能。我们的数据表明，星形胶质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。
