Overexpression of IL-1β by adenoviral-mediated gene transfer in the rat brain causes a prolonged hepatic chemokine response, axonal injury and the suppression of spontaneous behaviour
Overexpression of IL-1β by adenoviral-mediated gene transfer in the rat brain causes a prolonged hepatic chemokine response, axonal injury and the suppression of spontaneous behaviour
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DOI：
10.1016/j.nbd.2007.04.013
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发表时间：
2007-08-01
影响因子：
6.1
通讯作者：
Anthony, Daniel C.
中科院分区：
文献类型：
--
作者：
Campbell, Sandra J.;Deacon, Rob M. J.;Anthony, Daniel C.
急性脑损伤诱导趋化因子的早期和短暂的肝脏表达，其放大损伤反应并引起白细胞进入血液并随后进入脑和肝脏的运动。在这里，我们试图确定大脑内持续的损伤刺激是否会继续驱动肝脏趋化因子反应，以及它如何影响行为和CNS完整性。我们通过腺病毒介导的基因转移在大鼠脑中产生慢性IL-1 β表达，这导致慢性白细胞募集、轴突损伤和自发行为的长期抑制。在循环血液中无法检测到IL-1 β，但建立了慢性全身反应，包括肝脏和循环趋化因子的延长产生、白细胞增多、肝损伤、体重减轻、血清白蛋白降低和明显的肝脏白细胞募集。因此，肝趋化因子合成是活动性慢性CNS疾病的一个特征，并为抑制CNS炎症提供了一个可及的靶点。(c)2007年爱思唯尔公司All rights reserved.
Acute brain injury induces early and transient hepatic expression of chemokines, which amplify the injury response and give rise to movement of leukocytes into the blood and subsequently the brain and liver. Here, we sought to determine whether an ongoing injury stimulus within the brain would continue to drive the hepatic chemokine response and how it impacts on behaviour and CNS integrity. We generated chronic IL-1 beta expression in rat brain by adenoviral-mediated gene transfer, which resulted in chronic leukocyte recruitment, axonal injury and prolonged depression of spontaneous behaviour. IL-1 beta could not be detected in circulating blood, but a chronic systemic response was established, including extended production of hepatic and circulating chemokines, leukocytosis, liver damage, weight loss, decreased serum albumin and marked liver leukocyte recruitment. Thus, hepatic chemokine synthesis is a feature of active chronic CNS disease and provides an accessible target for the suppression of CNS inflammation. (c) 2007 Elsevier Inc. All rights reserved.