Selective increases in cytokine expression in the rat brain in response to striatal injection of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1
Selective increases in cytokine expression in the rat brain in response to striatal injection of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1
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DOI：
10.1016/s0169-328x(01)00211-x
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发表时间：
2001-09-30
期刊：
影响因子：
--
通讯作者：
Rothwell, NJ
中科院分区：
文献类型：
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作者：
Allan, SM;Harrison, DC;Rothwell, NJ
许多细胞因子有助于急性实验性神经变性。细胞因子反应可能有有害或有益的影响，这取决于时间分布和促炎和抗炎分子之间的平衡。我们最近的数据表明，当与强效兴奋毒素α -氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（S-AMPA）共同给药时，促炎细胞因子白细胞介素-1 β (IL-1 β)作用于大鼠大脑的特定部位（例如纹状体），导致远端皮质损伤。本研究的目的是利用逆转录聚合酶链式反应（RT-PCR: Taqman （TM）荧光探针）和酶联免疫吸附试验（ELISA）研究鼠纹状体和皮层中几种细胞因子同时表达的变化，这些细胞因子分别为载药、S-AMPA或人重组（hr） IL-1 β或S-AMPA与hil -1 β共注射。单独注射S-AMPA后8 h，同侧纹状体IL-6 mRNA表达增加，纹状体单独注射IL-1 β增加局部IL-1 β和IL-1ra mRNA表达。S-AMPA和hrIL-1 β共注射8 h后，同侧皮质IL-1 α、IL-1 β、IL-1ra、IL-6、IL-10和TNF α mRNA表达水平显著升高。皮层中IL-4的mRNA水平。治疗2 h和8 h后，两组间IL-18、TGF β和IFN γ均无显著差异。治疗8 h后，两组间IL-la和IL-6蛋白水平变化规律相似。这些数据表明，在hrIL-1 β和S-AMPA的作用下，细胞因子在远程细胞死亡区域的表达选择性增加。这些细胞因子可能与随后的损伤有关，进一步阐明它们的作用有助于未来几种急性神经退行性疾病的治疗策略。(C) 2001 Elsevier Science BY。版权所有。
A number of cytokines contribute to acute experimental neurodegeneration. The cytokine response can have detrimental or beneficial effects depending on the temporal profile and balance between pro- and anti- inflammatory molecules. Our recent data suggest that the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) acts at specific sites (e.g., the striatum) in the rat brain to cause distant cortical injury, when co-administered with the potent excitotoxin alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA). The objective of the present study was to investigate changes in the expression of several cytokines simultaneously in the rat striatum and cortex after intrastriatal administration of vehicle, S-AMPA or human recombinant (hr) IL-1 beta alone or S-AMPA co-injected with hrIL-1 beta using reverse transcription-polymerase chain reaction (RT-PCR: Taqman (TM) fluorogenic probes) and enzyme-linked immunosorbent assay (ELISA). Injection of S-AMPA alone increased IL-6 mRNA expression in the ipsilateral striatum after 8 h, whilst striatal injection of IL-1 beta alone increased local IL-1 beta and IL-1ra mRNAs. The levels of mRNA encoding IL-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-10 and TNF alpha were markedly elevated in the ipsilateral cortex 8 h after co-injection of S-AMPA and hrIL-1 beta. Cortical mRNA levels for IL-4. IL-18, TGF beta and IFN gamma were not significantly different between treatment groups after 2 h or 8 h. A similar pattern of change in the levels of IL-la and IL-6 protein was observed 8 h after treatment. These data demonstrate selective increases in the expression of cytokines in areas of remote cell death in response to administration of hrIL-1 beta and S-AMPA. Such cytokines may be involved in the ensuing damage, and further clarification of their actions could aid future therapeutic strategies for several acute neurodegenerative disorders. (C) 2001 Elsevier Science BY. All rights reserved.