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大鼠外周神经系统中促炎细胞因子和白细胞介素-10的mRNA的序贯表达:免疫介导的脱髓鞘与沃勒变性的比较。

Sequential expression of mRNA for proinflammatory cytokines and interleukin-10 in the rat peripheral nervous system: comparison between immune-mediated demyelination and Wallerian degeneration.

作者信息

Gillen C, Jander S, Stoll G

机构信息

Department of Neurology, Heinrich-Heine-Universität, Düsseldorf, Germany.

出版信息

J Neurosci Res. 1998 Feb 15;51(4):489-96. doi: 10.1002/(SICI)1097-4547(19980215)51:4<489::AID-JNR8>3.0.CO;2-8.

Abstract

This study examined the time course of mRNA levels of the proinflammatory cytokines interferon-gamma (IFNgamma), interleukin-1beta (IL1beta), interleukin-12 (IL12; p40 subunit), and the immunosuppressant interleukin-10 (IL10) by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) in rats with actively induced experimental autoimmune neuritis (EAN) and in distal stumps of crushed sciatic nerves undergoing Wallerian degeneration. In EAN IFNgamma- and IL1beta-mRNA peaked at the onset and acute phase of clinical disease. IL12p40-mRNA was upregulated later than IFNgamma-mRNA in the late acute phase from days 15 to 21. IL10-mRNA appeared concomitantly with the proinflammatory cytokines at day 11, but persisted at high levels into the clinical recovery phase. After nerve crush both IL1beta- and IL10-mRNA were rapidly upregulated in the distal stump at day 1 and slowly declined over the next 2 weeks. Significant levels of mRNA for IFNgamma could be found at days 4 and 7, whereas IL12p40-mRNA showed a biphasic induction. We provide evidence for a concomitant induction of pro- and anti-inflammatory cytokines in EAN. Moreover, the rapid upregulation in Wallerian degeneration suggests a more general role of cytokines in the biology of the peripheral nerve.

摘要

本研究通过半定量逆转录聚合酶链反应(RT-PCR)检测了主动诱导的实验性自身免疫性神经炎(EAN)大鼠以及正在经历沃勒变性的坐骨神经挤压远端残端中促炎细胞因子干扰素-γ(IFNγ)、白细胞介素-1β(IL1β)、白细胞介素-12(IL12;p40亚基)和免疫抑制剂白细胞介素-10(IL10)的mRNA水平随时间的变化过程。在EAN中,IFNγ和IL1β-mRNA在临床疾病的发作期和急性期达到峰值。IL12p40-mRNA在急性期后期(第15至21天)比IFNγ-mRNA上调得晚。IL10-mRNA在第11天与促炎细胞因子同时出现,但在临床恢复期一直维持在高水平。神经挤压后,IL1β和IL10-mRNA在第1天在远端残端迅速上调,并在接下来的2周内缓慢下降。在第4天和第7天可检测到显著水平的IFNγ mRNA,而IL12p40-mRNA表现出双相诱导。我们提供了EAN中促炎和抗炎细胞因子同时诱导的证据。此外,沃勒变性中的快速上调表明细胞因子在周围神经生物学中具有更广泛的作用。

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