Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide.
Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide.
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DOI：
10.1186/1742-2094-7-1
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发表时间：
2010-01-04
影响因子：
9.3
通讯作者：
Dorovini-Zis K
中科院分区：
文献类型：
--
作者：
Chui R;Dorovini-Zis K
趋化因子是中枢神经系统炎症的重要介质，能够激活白细胞整合素，并指导白细胞亚群迁移到抗原攻击部位。在这项研究中，我们研究了CCL 2（MCP-1）和CCL 3（MIP-1α）在体外人血脑屏障模型中的表达、释放和结合。应用免疫细胞化学和酶联免疫吸附试验研究了原代培养的人脑微血管内皮细胞（HBMEC）中β-趋化因子CCL 2和CCL 3的表达和细胞因子上调及释放的动力学。此外，这些趋化因子的基底和顶端内皮细胞表面的差异结合进行了评估，通过免疫电子显微镜。未经处理的HBMEC合成并释放低水平的CCL 2。CCL 3最低限度地表达，但不被静息HBMEC释放。用TNF-α、IL-1β、LPS以及TNF-α和IFN-γ的组合处理，而不是单独的IFN-γ，以时间依赖性方式显著上调两种趋化因子的表达和释放。释放的CCL 2和CCL 3分别结合到顶端和基底内皮表面。这种分布是逆转的精氨酸激活的HBMEC中，导致CCL 2的主要基础定位和CCL 3的顶端分布。由于脑内皮细胞是接触循环白细胞的第一个驻留CNS细胞，因此CCL 2和CCL 3在脑内皮上的表达、释放和呈递表明这些趋化因子在CNS炎症中调节炎性细胞穿过BBB的运输中具有重要作用。
Chemokines are emerging as important mediators of CNS inflammation capable of activating leukocyte integrins and directing the migration of leukocyte subsets to sites of antigenic challenge. In this study we investigated the expression, release and binding of CCL2 (MCP-1) and CCL3 (MIP-1α) in an in vitro model of the human blood-brain barrier. The kinetics of expression and cytokine upregulation and release of the β-chemokines CCL2 and CCL3 were studied by immunocytochemistry and enzyme-linked immunosorbent assay in primary cultures of human brain microvessel endothelial cells (HBMEC). In addition, the differential binding of these chemokines to the basal and apical endothelial cell surfaces was assessed by immunoelectron microscopy. Untreated HBMEC synthesize and release low levels of CCL2. CCL3 is minimally expressed, but not released by resting HBMEC. Treatment with TNF-α, IL-1β, LPS and a combination of TNF-α and IFN-γ, but not IFN-γ alone, significantly upregulated the expression and release of both chemokines in a time-dependent manner. The released CCL2 and CCL3 bound to the apical and basal endothelial surfaces, respectively. This distribution was reversed in cytokine-activated HBMEC resulting in a predominantly basal localization of CCL2 and apical distribution of CCL3. Since cerebral endothelial cells are the first resident CNS cells to contact circulating leukocytes, expression, release and presentation of CCL2 and CCL3 on cerebral endothelium suggests an important role for these chemokines in regulating the trafficking of inflammatory cells across the BBB in CNS inflammation.
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影响因子：
3.3
作者：
Chen, P;Shibata, M;Hofman, FM
通讯作者：
Hofman, FM
影响因子：
7.8
作者：
Andjelkovic, AV;Spencer, DD;Pachter, JS
通讯作者：
Pachter, JS
影响因子：
4.3
作者：
Cai, JP;Hudson, S;Chin, YH
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Chin, YH
影响因子：
5.3
作者：
Eugenin, EA;Osiecki, K;Berman, JW
通讯作者：
Berman, JW
影响因子：
3.3
作者：
Franciotta, D;Martino, G;Cosi, V
通讯作者：
Cosi, V