Global forebrain ischemia results in differential cellular expression of interleukin-1 beta (IL-1B) and its receptor at mRNA and protein level

被引:113
作者
Sairanen, TR
Lindsberg, PJ
Brenner, M
Siren, AL
机构
[1] NINCDS, STROKE BRANCH, BETHESDA, MD 20892 USA
[2] UNIV HELSINKI, DEPT NEUROL, HELSINKI, FINLAND
关键词
rats; global ischemia; interleukin-1; beta; interleukin-1 receptor (type I); in situ hybridization; immunohistochemistry;
D O I
10.1097/00004647-199710000-00013
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The mRNA expression of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) has been shown to be induced in neural elements during ischemia. It is not clear which cells generate the IL-1 beta mRNA and eventually synthesize IL-1 protein and which cells respond to this signaling by producing IL-1 receptors during ischemia. To clarify this question, rats were subjected to global ischemia by bilateral carotid occlusion and hypotension for 20 minutes, followed by reperfusion for 2 hours (n = 7), 8 hours (n = 7), or 24 hours (n = 7). Cryostat sections were hybridized using antisense oligonucleotide probes (30 dimer). Multiple cell markers were used in immunohistochemical staining to identify the cells expressing IL-1 beta and IL-1R protein. The sham animals (n = 5) showed no or only a weak expression of IL-1R or IL-1 beta mRNA. The number of IL-1 beta mRNA-expressing cells was significantly increased by 2 hours of reperfusion in several brain areas including cortex (12-fold compared with sham) and caudate-putamen (14-fold), and was maximally increased in most hippocampal regions by 8 hours of reperfusion (mean +/- SD of positive cells/field versus sham equivalent being 37.9 +/- 12.3 versus 4.0 +/- 3.3; 30.6 +/- 9.0 versus 3.1 +/- 2.3; 41.3 +/- 17.5 versus 2.9 +/- 1.9; in CA1; CA2; CA3/CA4 regions of the hippocampus, respectively). IL-1 beta mRNA signal was also intensified in the white matter areas, Changes in IL-1R mRNA were seen in the hippocampus (after 2 hours CA1: 16-fold; CA2: 17-fold; DG: 24-fold increase; and CA3/CA4: 10-fold increase after 8 hours), and the expression was prolonged especially in CA1 and CA2 regions up to 24 hours of reperfusion. The major cellular source of IL-1 beta protein was glia (astrocytes, oligodendrocytes, microglia, and scattered perivascular macrophages/monocytes), while neurons and sporadic microvascular endothelia showed IL-1R immunoreactivity. The data suggest that neurons in discrete areas vulnerable for selective neuronal death, and possibly the vascular endothelium, are target cells for ischemia-induced glial IL-1 beta production.
引用
收藏
页码:1107 / 1120
页数:14
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