Regulation of interleukin-1β by the interleukin-1 receptor antagonist in the glutamate-injured spinal cord:: Endogenous neuroprotection
Regulation of interleukin-1β by the interleukin-1 receptor antagonist in the glutamate-injured spinal cord:: Endogenous neuroprotection
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DOI：
10.1016/j.brainres.2008.07.035
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发表时间：
2008-09-22
期刊：
影响因子：
2.9
通讯作者：
McAdoo, David J.
中科院分区：
文献类型：
--
作者：
Liu, Song;Xu, Guo-Ying;McAdoo, David J.
细胞外谷氨酸的升高导致脊髓损伤（SCI）产生的细胞死亡和功能障碍，部分原因是通过激活神经毒性细胞因子白细胞介素-1 β（IL-1 β）。本研究探讨了IL-1 β的参与及其调节的内源性白细胞介素-1受体拮抗剂（IL-1 ra）在谷氨酸毒性后SCI谷氨酸，谷氨酸能激动剂和SCI对IL-1 β和IL-1 ra的水平有类似的影响。在脊髓挫伤或暴露于升高的谷氨酸后，IL-1 β的浓度首先随着IL-1 ra的降低而升高，然后两者以相反的方向变化。将谷氨酸激动剂NMDA和S-AMPA应用于脊髓引起的IL-1 β和IL-1 ra水平的变化与挫伤和谷氨酸产生的变化非常相似。谷氨酸拮抗剂MK 801和NBQX阻断了谷氨酸诱导的IL-1 β和IL-1 ra水平的变化。给予IL-1 β可升高IL-1 ra，给予IL-1 ra可降低IL-1 β水平。将IL-β注入脊髓受损的运动，并注入IL-1 ra改善谷氨酸诱导的运动障碍的恢复。我们推测，升高IL-1 ra通过降低IL-1 β水平以及阻断IL-1 β与其受体的结合来对抗SCI中IL-1 β引起的损伤。我们的研究结果表明，IL-1 β有助于脊髓损伤后的谷氨酸损伤;阻断IL-1 β可能有效地抵消谷氨酸毒性。(C)2008 Elsevier B. V.保留所有权利。
Elevation of extracellular glutamate contributes to cell death and functional impairments generated by spinal cord injury (SCI), in part through the activation of the neurotoxic cytokine interleukin-1 beta (IL-1 beta). This study examines the participation of IL-1 beta and its regulation by the endogenous interleukin-1 receptor antagonist (IL-1ra) in glutamate toxicity following SCI Glutamate, glutamatergic agonists and SCI had similar effects on levels of IL-1 beta and IL-1ra. Following spinal cord contusion or exposure to elevated glutamate, concentrations of IL-1 beta first increased as IL-1ra decreased, and both then changed in the opposite directions. Applying the glutamate agonists NMDA and S-AMPA to the spinal cord caused changes in IL-1 beta and IL-1ra levels very similar to those produced by contusion and glutamate. The glutamate antagonists MK801 and NBQX blocked the glutamate-induced changes in IL-1 beta and IL-1ra levels. Administering IL-1 beta elevated IL-1ra, and administering IL-1ra depressed IL-1 beta levels. Infusing IL-beta into the spinal cord impaired locomotion, and infusing IL-1ra improved recovery from glutamate-induced motor impairments. We hypothesize that elevating IL-1ra opposes the damage caused by IL-1 beta in SCI by reducing IL-1 beta levels as well as by blocking binding of IL-1 beta to its receptor. Our results demonstrate that IL-1 beta contributes to glutamate damage following SCI; blocking IL-1 beta may usefully counteract glutamate toxicity. (C) 2008 Elsevier B.V. All rights reserved.