Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors (p55 and p75) in the rat brain: A view from the blood-brain barrier
Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors (p55 and p75) in the rat brain: A view from the blood-brain barrier
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DOI：
10.1016/s0306-4522(99)00225-0
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Rivest, S
中科院分区：
文献类型：
--
作者：
Nadeau, S;Rivest, S
肿瘤坏死因子是一种有效的髓细胞激活剂，它通过两种细胞表面受体，p55和p75肿瘤坏死因子受体起作用。本研究描述了两种受体信使rna在基础条件下以及在全身注射细菌内毒素脂多糖和重组大鼠肿瘤坏死因子- α的反应下在大鼠大脑中的细胞分布。通过静脉注射肿瘤坏死因子α刺激，检测编码c-fos、环氧化酶-2酶和抑制因子kappa B α的信使RNA的时间相关性诱导，作为微血管神经元和细胞活化的指标。促炎细胞因子对下丘脑-垂体-肾上腺轴的影响通过测定促肾上腺皮质激素释放因子转录活性和血浆皮质酮水平来确定。在脑室周围器官、脉络膜丛、轻脑膜、室管膜内衬细胞和血管中检测到p55信使RNA的组成性表达，而在基础条件下，大脑中几乎检测不到p75转录本。免疫原性损伤导致屏障相关结构和血管中肿瘤坏死因子受体的上调，这一事件与微血管的强烈激活有关。事实上，静脉注射肿瘤坏死因子- α引发了血脑屏障细胞内抑制因子kappa B α和环氧化酶-2的快速和短暂转录，双标记技术提供了脑毛细血管内皮表达抑制因子kappa B α的解剖学证据。循环肿瘤坏死因子- α也能快速刺激参与自主神经控制的核中c-fos的表达，包括终纹床核、下丘脑室旁核、杏仁核中央核、孤立束核和延髓腹外侧核。脑室周围器官、终板血管器、皮层下器官、正中隆起和脑后区均检测到延迟的c-fos mRNA诱导。下丘脑室旁核显示促肾上腺皮质激素释放因子初级转录物的表达，这与静脉注射肿瘤坏死因子- α后1小时血浆皮质酮水平的急剧升高有关。综上所述，这些数据证明p55是中枢神经系统中最丰富的肿瘤坏死因子受体，并在屏障相关结构中表达。循环肿瘤坏死因子具有直接激活脑大血管和小毛细血管内皮的能力，可产生可溶性分子（如前列腺素），通过实质元件将信号传递。c-fos诱导核的模式表明，细胞因子诱导了复杂的神经元回路，以激活神经内分泌促肾上腺皮质激素释放因子和促肾上腺皮质激素轴，这是适当控制全身炎症反应的关键生理反应。(c) 1999年ibro。Elsevier Science Ltd.出版。
Tumor necrosis factor is a potent activator of myeloid cells, which acts via two cell-surface receptors, the p55 and p75 tumor necrosis factor receptors. The present study describes the cellular distribution of both receptor messenger RNAs across the rat brain under basal conditions and in response to systemic injection with the bacterial endotoxin lipopolysaccharide and recombinant rat tumor necrosis factor-alpha. Time-related induction of the messenger RNA encoding c-fos, cyclo-oxygenase-2 enzyme and the inhibitory factor kappa B alpha was assayed as an index of activated neurons and cells of the microvasculature by intravenous tumor necrosis factor-alpha challenge. The effect of the proinflammatory cytokine on the hypothalamic-pituitary-adrenal axis was determined by measuring the transcriptional activity of corticotropin-releasing factor and plasma corticosterone levels. Constitutive expression of p55 messenger RNA was detected in the circumventricular organs, choroid plexus, leptomeninges, the ependymal lining cells of the ventricular walls and along the blood vessels, whereas p75 transcript was barely detectable in the brain under basal conditions. Immunogenic insults caused up-regulation of both tumor necrosis factor receptors in barrier-associated structures, as well as over the blood vessels, an event that was associated with a robust activation of the microvasculature. Indeed, intravenous tumor necrosis factor-alpha provoked a rapid and transient transcription of inhibitory factor kappa B alpha and cyclo-oxygenase-2 within cells of the blood-brain barrier, and a dual-labeling technique provided the anatomical evidence that the endothelium of the brain capillaries expressed inhibitory factor kappa B alpha. Circulating tumor necrosis factor-alpha also rapidly stimulated c-fos expression in nuclei involved in the autonomic control, including the bed nucleus of the stria terminalis, the paraventricular nucleus of the hypothalamus, the central nucleus of the amygdala, the nucleus of the solitary tract and the ventrolateral medulla. A delayed c-fos mRNA induction was detected in the circumventricular organs, organum vascularis of the lamina terminalis, the subfornical organ, the median eminence and the area postrema. The paraventricular nucleus of the hypothalamus exhibited expression of corticotropin-releasing factor primary transcript that was associated with a sharp increase in the plasma corticosterone levels 1 h after intravenous tumor necrosis factor-alpha administration.Taken together, these data provide the evidence that p55 is the most abundant tumor necrosis factor receptor in the central nervous system and is expressed in barrier-associated structures. Circulating tumor necrosis factor has the ability to directly activate the endothelium of the brain's large blood vessels and small capillaries, which may produce soluble molecules (such as prostaglandins) to vehicle the signal through parenchymal elements. The pattern of c-fos-inducible nuclei suggests complex neuronal circuits solicited by the cytokine to activate neuroendocrine corticotropin-releasing factor and the corticotroph axis, a key physiological response for the appropriate control of the systemic inflammatory response. (C) 1999 IBRO. Published by Elsevier Science Ltd.