Neuroprotective actions of endogenous interleukin-1 receptor antagonist (IL-1ra) are mediated by glia
Neuroprotective actions of endogenous interleukin-1 receptor antagonist (IL-1ra) are mediated by glia
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作者：
Pinteaux, E;Rothwell, NJ;Boutin, H
促炎症细胞因子白介素1(IL-1)参与了缺血、兴奋毒性或创伤引起的神经细胞炎症和细胞死亡，而给予IL-1受体拮抗剂(IL-1ra)可减轻神经元损伤。本研究的目的是验证内源性IL-1ra在体内和体外具有神经保护作用的假说，并确定其作用机制。与野生型(WT)小鼠相比，缺乏IL-1Ra(IL-1Ra基因敲除(KO))的小鼠表现出由短暂性脑缺血引起的神经元损伤的急剧增加(梗塞面积增加3.6倍)。WT和IL-1Ra KO培养的皮层神经元的基底层细胞死亡相同，NMDA或AMPA(20mU M)处理使WT和IL-1Ra KO神经元的细胞死亡程度相同。然而，在IL-1Ra KO的神经胶质细胞-神经元共培养中，基础细胞和NMDA或AMPA诱导的细胞死亡显著高于WT小鼠。我们进一步表明，纯小胶质细胞培养，而不是纯星形胶质细胞培养，在NMDA或AMPA处理的原代神经元的条件培养液处理下，释放IL-1ra。提示小胶质细胞产生的内源性IL-1ra对脑缺血或兴奋性毒性具有神经保护作用。(C)2005年Wiley-Liss，Inc.
The pro-inflammatory cytokine interleukin-1 (IL-1), contributes to neuronal inflammation and cell death induced by ischemia, excitotoxicity, or trauma, while administration of IL-1 receptor antagonist (IL-1ra) reduces neuronal injury. The aim of the present study was to test the hypothesis that endogenous IL-1ra is neuroprotective in vivo and in vitro, and to identify its mechanism of actions. Mice lacking IL-1ra (IL-1ra knock-out (KO]) exhibited a dramatic increase in neuronal injury (3.6-fold increase in infarct size) induced by transient cerebral ischemia compared to wildtype (WT) animals. Basal cell death of cultured cortical neurons from WT and IL-1ra KO was identical, and treatment with NMDA or AMPA (20 mu M) increased cell death to the same extent in WT and IL-1ra KO neurons. However, basal and NMDA- or AMPA-induced cells death was significantly higher in glial-neuronal co-cultures from IL-1ra KO than from WT mice. We further showed that pure microglial cultures, but not pure astrocytes cultures, released IL-1ra in response to treatment with conditioned medium from NMDA- or AMPA-treated primary neurons. These results demonstrate that endogenous IL-1ra produced by microglia is neuroprotective in cerebral ischemia or excitotoxicity. (C) 2005 Wiley-Liss, Inc.