Differential regulation of membrane bound and soluble ICAM 1 in human endothelium and blood mononuclear cells: Effects of interferon beta-1a
Differential regulation of membrane bound and soluble ICAM 1 in human endothelium and blood mononuclear cells: Effects of interferon beta-1a
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DOI：
10.1080/15419060216305
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发表时间：
2002-09-01
影响因子：
--
通讯作者：
Trojano, M
中科院分区：
文献类型：
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作者：
Giorelli, M;De Blasi, A;Trojano, M
膜相关细胞间黏附分子1(MICAM 1)是白细胞与内皮细胞黏附的基础。可溶性细胞间黏附分子1(SICAM 1)存在于人血清中，被视为多发性硬化症(MS)患者疾病活动性的标志。在接受干扰素-β治疗的MS患者中检测到高水平的sICAM-1，但对sICAM-1的分子来源知之甚少。本研究探讨了干扰素-β-1a和其他诱导剂刺激人脐静脉内皮细胞(HUVECs)和单个核细胞(MNL)产生sICAM-1和MICAM-1的相互关系及其机制。我们发现MICAM-1的表达和sICAM-1的释放在这两种细胞类型中都有不同的调节。HUVECs和MNL都表达MICAM-1和sICAM-1的特异性mRNA，这些转录本的含量的改变导致了对ICAM-1亚型的调节。我们表明IFNbeta-1a是ICAM 1 RNA剪接机制的强大调节者。细胞间黏附分子1亚型的过度表达可能对多发性硬化的发生有一定的免疫调节作用。
The membrane-associated Intercellular Adhesion Molecule 1 (mICAM 1) is fundamental for adhesion of leukocytes to endothelial cells. A soluble form of ICAM 1 (sICAM 1) exists in the human serum, and is seen as marker of disease activity in patients suffering from Multiple Sclerosis (MS). High levels of sICAM 1 have been detected in MS patients benefiting from interferon beta (IFNbeta) treatment, but little is known on the molecular origins of sICAM 1. This study investigated the interrelationship and the mechanisms of production of sICAM 1 and mICAM 1 in human endothelium (Human Umbilical Vein Endothelial Cells, HUVECs) and mononuclear leukocytes (MNL) upon stimulation with IFNbeta-1a and other inducers. We found that the expression of mICAM 1 and the release of sICAM 1 are differentially regulated in both these cytotypes. HUVECs and MNL express specific mRNA for both mICAM 1 and sICAM 1, and modification of the content of each of these transcripts results in regulation of both the ICAM 1 isoforms. We show that IFNbeta-1a is strong regulator of the ICAM 1 RNA splicing machinery. Effect of IFNbeta-1a over expression of the ICAM 1 isoforms might have a relevant immunomoregulatory role in Multiple Sclerosis.