The effects of nickel and chromium on human keratinocytes:: Differences in viability, cell associated metal and IL-1α release

The effects of nickel and chromium on human keratinocytes:: Differences in viability, cell associated metal and IL-1α release
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DOI:
10.1016/j.tiv.2007.01.026
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发表时间:
2007-08-01
影响因子:
3.2
通讯作者:
Evans, Gareth S.
Evans, Gareth S.
中科院分区:
医学3区
文献类型:
--
作者:
Curtis, Angela;Morton, Jackie;Evans, Gareth S.

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本研究旨在评估铬和镍对作为人体皮肤体外模型的分离角质形成细胞的影响。从未知金属敏感性的健康志愿者皮肤样品(n = 10)中分离角质形成细胞,并与来自已知金属敏感性的患者活检组织的细胞(n = 7)进行比较。用浓度范围(0- 10,000 μ M)的镍和铬给药细胞,并测量细胞线粒体活性、生存力、金属摄取和细胞因子释放。还比较了原代与传代角质形成细胞的反应。通过非线性Hill Plot模型对来自原代和传代角质形成细胞的毒性数据进行统计分析。结果显示,与镍相比,六价铬的细胞毒性显著更强,与角质形成细胞的相关性更强,并诱导IL-1 α的剂量依赖性释放。显着差异,观察原代和传代角质形成细胞铬和镍的毒性和反应的变化。与斑贴试验阴性对照(n = 3)相比,在已知致敏活检患者样本(n = 4)中,未观察到铬或镍诱导的细胞毒性或细胞因子释放存在差异。这项研究的结果表明,人角质形成细胞在体外反应非常不同的铬和镍。皇冠版权所有(c)2007年出版的爱思唯尔有限公司保留所有权利。
This study was carried out to assess the effects of chromium and nickel upon isolated keratinocytes as an in vitro model of human skin. Keratinocytes were isolated from healthy volunteer skin samples of unknown metal sensitivity (n = 10) and were compared with cells from patient biopsies of known metal sensitivity (n = 7). Cells were dosed with a concentration range of nickel and chromium (0-10,000 mu M) and cellular mitochondrial activity, viability, metal uptake and cytokine release were measured. Responses of primary versus passaged keratinocytes were also compared. Toxicity data from primary and passaged keratinocytes was statistically analysed by the non-linear Hill Plot model. Results showed that hexavalent chromium was significantly more cytotoxic, associated more with keratinocytes and induced a dose dependant release of IL-1 alpha compared to nickel. Significant differences were observed between primary and passaged keratinocytes with regard to the toxicity of chromium and nickel and variation of response. No differences were observed in the cytotoxicity or cytokine release induced by chromium or nickel for the known sensitised biopsy patient samples (n = 4) compared to patch test negative controls (n = 3). The results from this study suggest human keratinocytes in vitro respond very differently to chromium and nickel. Crown Copyright (c) 2007 Published by Elsevier Ltd. All rights reserved.