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Selective increases in cytokine expression in the rat brain in response to striatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1.
Allan S, Harrison D, Read S, Collins B, Parsons A, Philpott K, Rothwell NJ
Brain Res Mol Brain Res. 2001;93( 2):180-9.
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Abstract
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-1beta (IL-1beta) 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-1beta alone or S-AMPA co-injected with hrIL-1beta using reverse transcription-polymerase chain reaction (RT-PCR; Taqman 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-1beta alone increased local IL-1beta and IL-1ra mRNAs. The levels of mRNA encoding IL-1alpha, IL-1beta, IL-1ra, IL-6, IL-10 and TNFalpha were markedly elevated in the ipsilateral cortex 8 h after co-injection of S-AMPA and hrIL-1beta. Cortical mRNA levels for IL-4, IL-18, TGFbeta and IFNgamma were not significantly different between treatment groups after 2 h or 8 h. A similar pattern of change in the levels of IL-1alpha 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-1beta 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.
Keyword(s)
Animals; Human; Male; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Support, Non-U.S. Gov't; biosynthesis: Cytokines; biosynthesis: Interleukin-1; biosynthesis: Interleukins; biosynthesis: Nerve Tissue Proteins; biosynthesis: RNA, Messenger; biosynthesis: Transforming Growth Factor beta; biosynthesis: Tumor Necrosis Factor; chemically induced: Nerve Degeneration; drug effects: Apoptosis; drug effects: Corpus Striatum; drug effects: Gene Expression Regulation; genetics: DNA, Complementary; metabolism: Cerebral Cortex; pharmacology: Excitatory Amino Acid Agonists; pharmacology: Recombinant Fusion Proteins; pharmacology: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid