T lymphocytes conditioned with Interferon β induce membrane and soluble VCAM on human brain endothelial cells
T lymphocytes conditioned with Interferon β induce membrane and soluble VCAM on human brain endothelial cells
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DOI：
10.1016/s0165-5728(01)00253-3
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发表时间：
2001-04-02
影响因子：
3.3
通讯作者：
Antel, JP
中科院分区：
文献类型：
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作者：
Calabresi, PA;Prat, A;Antel, JP
血管细胞粘附分子（VCAM）-1在介导炎性细胞粘附和迁移中起关键作用。调节膜（m）VCAM及其裂解的对应物可溶性（s）VCAM表达的因素知之甚少。我们以前证明，血清sVCAM水平增加的多发性硬化症（MS）患者用干扰素β 1b（IFN β 1b），这与减少钆增强病变的磁共振成像。然而，随后的研究表明IFN β并不直接诱导内皮细胞上的VCAM表达。我们在此证明，与IFN β条件T细胞共培养诱导人脑内皮细胞（HBEC）上的mVCAM。此外，发生sVCAM的快速脱落，这反映了体内IFN β治疗后的反应。VCAM诱导部分通过肿瘤坏死因子（TNF）α介导，并可被sTNF受体消除。还可以使用IFN β-条件化T细胞在星形胶质瘤系上诱导VCAM，这表明该作用对HBEC不是特异性的。动力学研究表明sVCAM与mVCAM的比率随时间增加，这可能有助于IFN β在患者中的最终治疗效果。这些数据对于了解体内血脑屏障发生的事件以及确定MS中IFN β的作用机制具有重要意义。（C）2001 Elsevier Science B. V.保留所有权利。
Vascular cell adhesion molecule (VCAM)-1 plays a critical role in mediating inflammatory cell adhesion and migration. Factors regulating the expression of membrane (m)VCAM and its cleaved counterpart soluble (s)VCAM are poorly understood. We previously demonstrated that serum sVCAM levels are increased in multiple sclerosis (MS) patients treated with interferon beta 1b (IFN beta 1b), which correlated with a reduction in gadolinium enhancing lesions on magnetic resonance imaging. However, subsequent studies have shown that IFN beta does not directly induce VCAM expression on endothelial cells. We demonstrate here that co-culture with IFN beta -conditioned T cells induces mVCAM on human brain endothelial cells (HBEC). Further, rapid shedding of sVCAM occurs, which mirrors the response after in vivo IFN beta treatment. The VCAM induction is mediated partially through tumor necrosis factor (TNF)alpha and can be abrogated by sTNF receptor. VCAM could also be induced on astroglioma lines using IFN beta -conditioned T cells, which suggests the effect is not specific for HBEC. Kinetic studies demonstrated an increase in the sVCAM to mVCAM ratio over time, which may contribute to the ultimate therapeutic effect of IFN beta in patients. These data have important implications for understanding the events occurring at the blood brain barrier in vivo, and for determining the mechanism of action of IFN beta in MS. (C) 2001 Elsevier Science B.V. All rights reserved.