Schoeters Elke, Verheyen Geert R, Nelissen Inge, Van Rompay An R, Hooyberghs Jef, Van Den Heuvel Rosette L, Witters Hilda, Schoeters Greet E R, Van Tendeloo Vigor F I, Berneman Zwi N
Flemish Institute for Technological Research (VITO), Centre of Expertise in Environmental Toxicology, Boeretang 200, 2400 Mol, Belgium.
Mol Immunol. 2007 May;44(12):3222-33. doi: 10.1016/j.molimm.2007.01.031. Epub 2007 Mar 19.
The assessment of the skin sensitising capacity of chemicals is up to now investigated using in vivo animal tests. However there has been an increasing public and governmental concern regarding the use of animals for chemical screening. This has raised the need for the development of validated in vitro alternatives. Langerhans cells are potent antigen-presenting cells that play a crucial role in the development of allergic contact dermatitis. We used CD34(+) progenitor-derived dendritic cells from cord blood as an in vitro alternative for Langerhans cells. The cells were exposed to four contact allergens (nickel sulphate, dinitrochlorobenzene, oxazolone and eugenol) and two irritants (sodium dodecyl sulphate and benzalkonium chloride) for 3, 6, 12 and 24h. Using microarray analyses we revealed a set of 25 genes with an altered gene expression pattern after exposure to allergens and not to irritants. Five out of these 25 genes were selected and their gene expression changes were confirmed with real-time reverse transcriptase polymerase chain reaction. The list of 25 genes represent valuable candidates to be further evaluated for their capacity to predict the sensitizing potential of different classes of chemicals in studies using a more extended set of (non) allergic substances.
目前,化学物质皮肤致敏能力的评估是通过体内动物试验进行的。然而,公众和政府对将动物用于化学物质筛选的关注度日益增加。这就引发了对开发经过验证的体外替代方法的需求。朗格汉斯细胞是强大的抗原呈递细胞,在过敏性接触性皮炎的发展中起关键作用。我们使用来自脐带血的CD34(+)祖细胞衍生的树突状细胞作为朗格汉斯细胞的体外替代物。将这些细胞暴露于四种接触性变应原(硫酸镍、二硝基氯苯、恶唑酮和丁香酚)和两种刺激物(十二烷基硫酸钠和苯扎氯铵)中3、6、12和24小时。通过微阵列分析,我们发现一组25个基因在暴露于变应原而非刺激物后基因表达模式发生了改变。从这25个基因中选择了5个,并通过实时逆转录聚合酶链反应确认了它们的基因表达变化。这25个基因的列表代表了有价值的候选基因,在使用更广泛的(非)过敏物质组进行的研究中,可进一步评估它们预测不同类化学物质致敏潜力的能力。