Molecular and functional analysis of Shiga toxin-induced response patterns in human vascular endothelial cells
Molecular and functional analysis of Shiga toxin-induced response patterns in human vascular endothelial cells
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DOI：
10.1182/blood-2002-10-3301
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发表时间：
2003-08-15
期刊：
影响因子：
20.3
通讯作者：
Gunzer, F
中科院分区：
文献类型：
--
作者：
Matussek, A;Lauber, J;Gunzer, F
肠出血性大肠杆菌（EHEC）是导致溶血性尿毒症综合征（HUS）的主要原因，其特征是微血管致病性溶血性贫血、血小板减少症和急性肾功能衰竭。肠出血性大肠杆菌产生一种或多种志贺毒素（Stx1和Stx2），据推测，Stx唯一相关的生物活性是通过抑制蛋白质合成而破坏细胞。然而，最近的数据表明，体内细胞因子环境可能决定了当暴露于Stxs时内皮细胞是存活还是凋亡/坏死。在这项研究中，我们分析了受亚抑制浓度Stxs刺激的人内皮细胞的全基因组表达模式，以表征与溶血性尿毒综合征血管病理相关的基因组表达程序。我们发现Stxs引起的基因表达变化很少，但可重复。本研究中报道的大多数基因编码趋化因子和细胞因子，这可能有助于在肠出血性大肠杆菌疾病患者中观察到宿主内皮细胞的多方面炎症反应。此外，我们的数据首次提供了流行病学上公认的Stx2比Stx1具有更高致病性的分子见解。(C) 2003年由美国血液病学会出版。
Enterohemorrhagic Escherichia coli (EHEC) is the major cause of hemolyticuremic syndrome (HUS) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. EHEC produces one or more Shiga toxins (Stx1 and Stx2), and it was assumed that Stx's only relevant biologic activity was cell destruction through inhibition of protein synthesis. However, recent data indicate that in vivo the cytokine milieu may determine whether endothelial cells survive or undergo apoptosis/necrosis when ex posed to Stxs. In this study, we analyzed the genome-wide expression patterns of human endothelial cells stimulated with subinhibitory concentrations of Stxs in order to characterize the genomic expression program involved in the vascular pathology of HUS. We found that Stxs elicited few, but reproducible, changes in gene expression. The majority of genes reported in this study encodes for chemokines and cytokines, which might contribute to the multifaceted inflammatory response of host endothelial cells observed in patients suffering from EHEC disease. In addition, our data provide for the first time molecular insights into the epidemiologically well-established higher pathogenicity of Stx2 over Stx1. (C) 2003 by The American Society of Hematology.