Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactiviity: Relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli
Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactiviity: Relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli
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DOI：
10.1002/cne.20052
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发表时间：
2004-04-19
影响因子：
2.5
通讯作者：
Blomqvist, A
中科院分区：
文献类型：
--
作者：
Konsman, JP;Vigues, S;Blomqvist, A
白细胞介素- β (il -1 β)被认为通过在血脑屏障（BBB）诱导前列腺素，在疾病期间作用于大脑，诱导发烧、神经内分泌激活和行为改变。然而，尽管IL-1 β在脑血管细胞中诱导前列腺素合成酶环氧化酶-2 (COX-2)，但没有研究证实这些细胞中存在IL-1受体1型（IL-1R1）蛋白。此外，尽管在给予il -1 β或细菌脂多糖（LPS）后，COX抑制剂会减弱视前和室旁下丘脑中活化标记物c-Fos的表达，但它们不会改变已知表达前列腺素受体的其他结构中c-Fos的诱导。因此，本研究试图确定IL-1R1蛋白是否在大鼠脑血管系统中存在并起作用。此外，将IL-1R1蛋白的分布与il -1 β和lps诱导的COX-2表达进行比较。il - 1r1免疫反应性血管周围细胞多见于脉络膜丛和脑膜。il - 1r1免疫反应血管遍布整个大脑，但集中在视前区、皮质下器官、视上下丘脑，以及较小程度的室旁下丘脑、皮质、孤立束核和腹侧髓质。血管IL-1R1-ir与内皮细胞标志物相关，在小动脉中未发现，并且与il -1 - β刺激时磷酸化的c-jun和抑制因子kappaB mRNA的诱导模式相对应，并与外周il -1 - β或lps诱导的COX-2表达共定位。这些观察结果表明，功能性IL-1R1在脑小静脉内皮细胞中表达，表明血管IL-1R1分布是决定感染期间血脑屏障前列腺素依赖性脑结构激活的重要因素。(C) 2004 Wiley-Liss, Inc。
Interleukin-beta (IL-1beta) is thought to act on the brain to induce fever, neuroendocrine activation, and behavioral changes during disease through induction of prostaglandins at the blood-brain barrier (BBB). However, despite the fact that IL-1beta induces the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in brain vascular cells, no study has established the presence of IL-1 receptor type 1 (IL-1R1) protein in these cells. Furthennore, although COX inhibitors attenuate expression of the activation marker c-Fos in the preoptic and paraventricular hypothalamus after administration of IL-1beta or bacterial lipolysaccharide (LPS), they do not alter c-Fos induction in other structures known to express prostaglandin receptors. The present study thus sought to establish whether IL-1R1 protein is present and functional in the rat cerebral vasculature. In addition, the distribution of IL-1R1 protein was compared to IL-1beta- and LPS-induced COX-2 expression. IL-1R1-immunoreactive perivascular cells were mostly found in choroid plexus and meninges. IL-1R1immunoreactive vessels were seen throughout the brain, but concentrated in the preoptic area, subfornical organ, supraoptic hypothalamus, and to a lesser extent in the paraventricular hypothalamus, cortex, nucleus of the solitary tract, and ventrolateral medulla. Vascular IL-1R1-ir was associated with an endothelial cell marker, not found in arterioles, and corresponded to the induction patterns of phosphorylated c-jun and inhibitory-factor kappaB mRNA upon IL-1beta stimulation, and colocalized with peripheral IL-1beta- or LPS-induced COX-2 expression. These observations indicate that functional IL-1R1s are expressed in endothelial cells of brain venules and suggest that vascular IL-1R1 distribution is an important factor determining BBB prostaglandin-dependent activation of brain structures during infection. (C) 2004 Wiley-Liss, Inc.