Kainic acid induced expression of interleukin-1 receptor antagonist mRNA in the rat brain.
The endogenous interleukin-1 receptor antagonist (IL-1ra), a protein with partial homology with the proinflammatory cytokine interleukin-1beta (IL-1beta), prevents binding of IL-1beta to the signalling receptor. Exogenous IL-1ra has been shown to reduce the neuronal damage occurring after excitotoxic amino acid administration and ischemia. In the present study, in situ hybridization histochemistry was employed to investigate the regulation of endogenous IL-1ra mRNA expression in the rat brain after peripheral administration of kainic acid (10 mg/kg). IL-1ra mRNA expression was markedly induced in the hippocampus, thalamus, amygdala, piriform cortex, perirhinal cortex, entorhinal cortex, and to a lesser extent in the hypothalamus, and parietal and temporal cortex. The expression was first detected at 5 h after the kainic acid administration and it was markedly increased at 24 h. No signal was detected at 4 days after the injection. The majority of the cells expressing IL-1ra mRNA displayed the morphological characteristics of microglia. Expression of IL-1ra mRNA in neurons occurred mainly in the piriform and perirhinal cortex. The distribution pattern of IL-1ra mRNA expressing microglia-like cells was similar to that of cells labelled with ED1, a marker for activated microglia. The induction of IL-1ra mRNA expression may represent an endogenous response to balance IL-1 receptor mediated activity in the brain following kainic acid administration, conceivably to elicit neuroprotective and/or antiinflammatory effects.
Department of Clinical Neuroscience and Family Medicine, Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Novum, S-141 86, Huddinge, Sweden.
C
C
Eriksson
B
B
Winblad
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M
Schultzberg
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D053590:Interleukin 1 Receptor Antagonist Protein; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009928:Organ Specificity; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D053590:Interleukin 1 Receptor Antagonist Protein; D015347:RNA Probes; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D007608:Kainic Acid