Identification of gene expression changes induced by chemical allergens in dendritic cells: Opportunities for skin sensitization testing
Identification of gene expression changes induced by chemical allergens in dendritic cells: Opportunities for skin sensitization testing
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DOI：
10.1038/sj.jid.5700319
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发表时间：
2006-08-01
影响因子：
6.5
通讯作者：
Gerberick, G. Frank
中科院分区：
文献类型：
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作者：
Gildea, Lucy A.;Ryan, Cindy A.;Gerberick, G. Frank
皮肤树突状细胞（dc）在过敏原摄取和处理后的细胞变化是皮肤致敏的关键事件。在这里，我们描述了一套选择标准的发展，从先前用二硝基苯磺酸处理的人类外周血源性（外周血单个核细胞(PBMCs)-DCs）的微阵列分析中得出潜在靶基因列表，用于预测皮肤致敏化学物质。根据这些标准，使用扩展的化学数据集（包括5种皮肤刺激物和11种接触性过敏原）对目标基因进行了探索性评估。用不同浓度的化学物质处理pbmc - dcs 24小时，通过实时PCR分析检测每种情况下多达60个基因的表达。观察到许多基因在过敏原诱导下表达的一致变化，并通过分析非致敏化学物质处理的dc中的相同基因来进一步确定目标的优先级，以确定其对皮肤致敏的特异性。对多种化学过敏原、刺激物和非致敏剂的实时PCR分析已经鉴定出10个基因，这些基因表现出可重复的高水平选择性、特异性和动态范围，为鉴定皮肤致敏化学物质提供了可靠和敏感的替代方法基础。
Cellular changes within resident skin dendritic cells (DCs) after allergen uptake and processing are critical events in the acquisition of skin sensitization. Here we describe the development of a set of selection criteria to derive a list of potential target genes from previous microarray analyses of human peripheral blood-derived ( peripheral blood mononuclear cells (PBMCs)-DCs) treated with dinitrobenzene sulfonic acid for predicting skin-sensitizing chemicals. Based on those criteria, a probing evaluation of the target genes has been conducted using an extended chemical data set, comprising five skin irritants and 11 contact allergens. PBMCs-DCs were treated for 24 hours with various concentrations of chemicals and in each instance the expression of up to 60 genes was examined by real-time PCR analysis. Consistent allergen-induced changes in the expression of many genes were observed and further prioritization of the targets was conducted by analysis of the same genes in DCs treated with non-sensitizing chemicals to determine their specificity for skin sensitization. Real-time PCR analyses of multiple chemical allergens, irritants, and non-sensitizers have identified 10 genes that demonstrate reproducibly high levels of selectivity, specificity, and dynamic range consistent with providing the basis for robust and sensitive alternative approaches for the identification of skin-sensitizing chemicals.