Immunohistochemical localization of interleukin-1beta, interleukin-1 receptor antagonist and interleukin-1beta converting enzyme/caspase-1 in the rat brain after peripheral administration of kainic acid.
The temporal and anatomical distribution of members of the interleukin-1 system in the rat brain following intraperitoneal kainic acid administration was studied in relation to neurodegeneration as detected with in situ end labelling. Kainic acid administration (10 mg/kg, i.p.) resulted in the induced expression of interleukin-1beta, interleukin- receptor antagonist and caspase-1p10 immunoreactivity in areas known to display neuronal and tissue damage upon excitotoxic lesions. The induction of these proteins was transient. Interleukin-1 immunoreactivity appeared at 5 h, and the interleukin-1 receptor antagonist-immunoreactive cells were first detected at 12 h, whereas the induction of caspase- 1p10 expression was first detected 24 h after kainic acid injection. Double labelling with the microglial marker Ox42 confirmed that both interleukin-1beta and interleukin-1 receptor antagonist were mainly localized in microglial cells. The regional distribution of in situ end-labelled neurons was similar to the distribution of cells expressing interleukin-1beta and interleukin-1 receptor antagonist, whereas the distribution of caspase-1 was more limited. The in situ end-labelled neurons, were, similarly to the interleukin-1beta-positive cells, first detected at 5 h, which is earlier than the induction of caspase-1. Our results show that the induction of IL-1beta and IL-1 receptor antagonist proteins after kainic acid are closely associated with the temporal as well as the anatomical distribution of in situ end-labelled neurons, whereas the induction of caspase-1 protein exhibited a delayed temporal profile and limited distribution. Since cytokine production occurs in activated microglial cells, the inflammatory component seems to be a strong mediator of this type of excitotoxic damage. The late onset of the caspase-1 expression would seem to indicate that this enzyme has no fundamental role in directly causing neuronal cell death induced by systemic kainic acid.
Eriksson
C
C
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge Hospital, Novum, Sweden.
Van Dam
A M
AM
Lucassen
P J
PJ
Bol
J G
JG
Winblad
B
B
Schultzberg
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D020170:Caspase 1 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000737:chemistry / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics
D018690:Excitatory Amino Acid Agonists; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D009419:Nerve Tissue Proteins; D012795:Sialoglycoproteins; D020170:Caspase 1; D007608:Kainic Acid