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

被引:20
作者
Allan, SM
Harrison, DC
Read, S
Collins, B
Parsons, AA
Philpott, K
Rothwell, NJ
机构
[1] Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England
[2] GlaxoSmithKline, Neurol Res, Harlow CM19 5AW, Essex, England
来源
MOLECULAR BRAIN RESEARCH | 2001年 / 93卷 / 02期
基金
英国医学研究理事会;
关键词
excitotoxicity; cell death; S-AMPA; cytokines;
D O I
10.1016/S0169-328X(01)00211-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:180 / 189
页数:10
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