Cytotoxic effect of Shiga toxin-2 holotoxin and its B subunit on human renal tubular epithelial cells

Cytotoxic effect of Shiga toxin-2 holotoxin and its B subunit on human renal tubular epithelial cells
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DOI:
10.1016/j.micinf.2005.07.005
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发表时间:
2006-02-01
影响因子:
5.8
通讯作者:
Ibarra, C
Ibarra, C
中科院分区:
医学3区
文献类型:
--
作者:
Creydt, VP;Silberstein, C;Ibarra, C

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产志贺毒素的大肠杆菌产生水样腹泻、出血性结肠炎和溶血性尿毒症综合征(HUS)。在阿根廷,溶血性尿毒综合征是儿童急性肾衰竭的最常见原因。本研究的目的是检测Stx2型(Stx2全毒素)及其B亚基(Stx2 B亚基)在存在和不存在炎症因子的情况下对人肾小管上皮细胞(HRTEC)的细胞毒性。检测细胞形态、细胞活力、蛋白合成及凋亡。HRTEC对Stx2全毒素和Stx2 B亚基均具有剂量依赖性和时间依赖性。IL-1、LPS和丁酸盐增加了Stx介导的细胞毒性,而TNF、IL-6和IL-8没有增加。Stx2 B亚基的作用在剂量高于Stx2全毒剂量时出现。虽然这些作用的生理重要性尚不清楚,但重要的是要意识到B亚基的任何潜在毒性活性,因为它已被提议用于疫苗。(c) 2005 Elsevier SAS。版权所有。
Shiga toxin-producing Escherichia coli produces watery diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome (HUS). In Argentina, HUS is the most common cause of acute renal failure in children. The purpose of the present study was to examine the cytotoxicity of Stx type 2 (Stx2 holotoxin) and its B subunit (Stx2 B subunit) on human renal tubular epithelial cells (HRTEC), in the presence and absence of inflammatory factors. Cell morphology, cell viability, protein synthesis and apoptosis were measured. HRTEC are sensitive to both Stx2 holotoxin and Stx2 B subunit in a dose- and time-dependent manner. IL-1, LPS and butyrate but not TNF, IL-6 and IL-8, increased the Stx mediated cytotoxicity. The effects of Stx2 B subunit appear at doses higher than those used for Stx2 holotoxin. Although the physiological importance of these effects is not clear, it is important to be aware of any potentially toxic activity in the B subunit, given that it has been proposed for use in a vaccine. (c) 2005 Elsevier SAS. All rights reserved.