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首页> 外文期刊>Clinical and experimental allergy : >Gene expression studies in cultured dendritic cells: new indicators for the discrimination of skin sensitizers and irritants in vitro.
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Gene expression studies in cultured dendritic cells: new indicators for the discrimination of skin sensitizers and irritants in vitro.

机译：培养的树突状细胞中的基因表达研究：体外鉴别皮肤敏化剂和刺激物的新指标。

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BACKGROUND: The replacement of animal tests for the detection of the sensitizing potential of chemicals is of great importance due to current legislation. One promising approach for the development of an in vitro assay is the exposure of immature dendritic cells (iDCs) to contact sensitizers and irritants, followed by an analysis of the maturation status of the cells. OBJECTIVE: The aim of this study was to further investigate the performance of our previously developed targeted microarray, the immune toxicity chip. In addition, we aimed to identify new marker genes for the discrimination of allergens and irritants using whole-genome microarrays. METHODS: Monocyte-derived iDCs were exposed to contact sensitizers and irritants in concentrations resulting in 10-20% cytotoxicity, as determined by dose-response curves. Changes in gene expression were analysed using the immune toxicity chip and a commercially available whole-genome microarray. RESULTS: Using the immune toxicity chip, we could identify a panel of marker genes suitable to discriminate strong allergens and irritants. Analysis with the whole-genome array revealed additional genes that are differentially expressed after allergen exposure, but not after irritant exposure. Hierarchical clustering of these genes showed distinct groups representing the different chemicals. CONCLUSION: Here we show that our test system based on an immune-specific microarray is suitable for the discrimination of strong allergens and irritants. Genes detected as differentially expressed with the whole-genome array and previously not connected to the maturation process of DCs might be suitable candidate genes for the identification of weaker sensitizers.
机译：背景：由于目前的立法，更换动物试验以检测化学物质的潜在增感作用非常重要。开发体外测定的一种有前途的方法是使未成熟树突状细胞（iDC）接触接触性敏化剂和刺激物，然后分析细胞的成熟状态。目的：本研究的目的是进一步研究我们先前开发的靶向微阵列（免疫毒性芯片）的性能。此外，我们旨在使用全基因组微阵列识别新的标记基因，以区分过敏原和刺激物。方法：单核细胞衍生的iDCs暴露于接触敏化剂和刺激物，其浓度可导致10-20％的细胞毒性，这通过剂量反应曲线确定。使用免疫毒性芯片和市售全基因组微阵列分析基因表达的变化。结果：使用免疫毒性芯片，我们可以鉴定出一组适合区分强力过敏原和刺激物的标记基因。使用全基因组阵列进行的分析揭示了其他基因，这些基因在暴露于变应原后差异表达，但在暴露于刺激性后则差异表达。这些基因的层次聚类显示出代表不同化学物质的不同组。结论：在这里我们表明基于免疫特异性微阵列的测试系统适合区分强力过敏原和刺激性物质。检测到的与全基因组阵列差异表达的基因，以前未与DC的成熟过程相关的基因可能是鉴定较弱敏化剂的合适候选基因。

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