Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis
Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis
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DOI：
10.1177/1352458509358189
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发表时间：
2010-03-01
影响因子：
5.8
通讯作者：
Foerster, Carola Y.
中科院分区：
文献类型：
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作者：
Blecharz, Kinga G.;Haghikia, Aiden;Foerster, Carola Y.
血脑屏障完整性受损是活动性多发性硬化症（MS）的主要标志。脑内皮紧密连接蛋白和基因表达的改变发生在神经炎症的早期，但其潜在的机制知之甚少。在这项研究中，我们分析了MS患者血清的屏障损害作用和糖皮质激素对体外血脑屏障完整性的屏障恢复作用。将cEND小鼠脑微血管内皮细胞单层与来自疾病活动期或复发患者的血清一起孵育。将数据与糖皮质激素地塞米松单独或与MS血清组合对屏障完整性的影响进行比较。紧密连接蛋白水平和基因表达与屏障完整性一起进行评价。我们揭示了下调的claudin-5和occludin蛋白和mRNA，并伴随上调的基质金属蛋白酶MMP-9的表达后，与血清从活动性疾病和缓解，也是一个较小的重建与地塞米松治疗的屏障功能。此外，我们首次描述了cEND细胞与MS缓解期患者血清孵育后claudin-5和occludin蛋白的下调。我们的研究结果揭示了MS血清对血脑屏障完整性的直接和差异性影响。
Compromised blood-brain barrier integrity is a major hallmark of active multiple sclerosis (MS). Alterations in brain endothelial tight junction protein and gene expression occur early during neuroinflammation but there is little known about the underlying mechanisms. In this study, we analysed barrier compromising effects of sera from MS patients and barrier restoring effects of glucocorticoids on blood-brain barrier integrity in vitro. cEND murine brain microvascular endothelial cell monolayers were incubated with sera from patients in active phase of disease or in relapse. Data were compared with effects of the glucocorticoid dexamethasone alone or in combination with MS sera on barrier integrity. Tight junction protein levels and gene expression were evaluated concomitant with barrier integrity. We reveal down-regulation of claudin-5 and occludin protein and mRNA and an accompanying upregulation in expression of matrix metalloproteinase MMP-9 after incubation with serum from active disease and remission and also a minor reconstitution of barrier functions related to dexamethasone treatment. Moreover, we for the first time describe downregulation of claudin-5 and occludin protein after incubation of cEND cells with sera from patients in remission phase of MS. Our findings reveal direct and differential effects of MS sera on blood-brain barrier integrity.