Understanding the skin sensitization capacity of ascaridole: a combined study of chemical reactivity and activation of the innate immune system (dendritic cells) in the epidermal environment
Understanding the skin sensitization capacity of ascaridole: a combined study of chemical reactivity and activation of the innate immune system (dendritic cells) in the epidermal environment
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了解蛔苷的皮肤致敏能力：表皮环境中化学反应性和先天免疫系统（树突状细胞）激活的综合研究
DOI：
10.1007/s00204-019-02444-3
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发表时间：
2019
影响因子：
6.1
通讯作者：
Gimenez- Arnau
中科院分区：
文献类型：
--
作者：
Silva e Sousa;Vileno;Lichter;Lepoittevin;Blömeke;Gimenez- Arnau
为了提高与皮肤接触的化学品的可能过敏性的预测，上游事件的调查，需要更好地了解过敏反应的启动所涉及的分子机制。蛔虫素是导致皮肤对老化茶树油敏感的化合物之一，它降解为中间体，这些中间体通过涉及自由基物种的不同机制进化。我们的目的是通过评估对氨基酸的反应性概况，确定是否在重建的人表皮（RHE）模型中形成自由基及其生物学特性来激活免疫系统，即在人HaCaT角质形成细胞和RHE的天然背景下的树突状细胞，来拓宽有关来自蛔虫素的自由基中间体对皮肤致敏过程的贡献的知识。电子顺磁共振结合EpiSkin™ RHE中的自旋捕获证实了在表皮组织中由10 mM浓度的蛔虫素形成C-自由基，而对氨基酸的反应性研究显示由蛔虫素的自由基重排产生的亲电中间体作为主要反应性物质。基于共刺激分子CD 86和粘附分子CD 54的细胞表面表达，用低微摩尔浓度处理后，与HaCaT共培养的THP-1细胞作为树突状细胞的替代物的活化显著上调。将THP-1细胞放置在RHE下方允许我们监测在表皮皮肤环境中产生自由基和/或蛋白抗原的浓度中的哪一个促进树突状细胞的活化。我们检测到局部RHE应用浓度高达30 mM的蛔虫素后（t= 24 h），CD 86/CD 54没有显著上调，但在60 mM后明显上调。
To improve the prediction of the possible allergenicity of chemicals in contact with the skin, investigations of upstream events are required to better understand the molecular mechanisms involved in the initiation of allergic reactions. Ascaridole, one of the compounds responsible for skin sensitization to aged tea tree oil, degrades into intermediates that evolve via different mechanisms involving radical species. We aimed at broadening the knowledge about the contribution of radical intermediates derived from ascaridole to the skin sensitization process by assessing the reactivity profile towards amino acids, identifying whether free radicals are formed in a reconstructed human epidermis (RHE) model and their biological properties to activate the immune system, namely dendritic cells in their natural context of human HaCaT keratinocytes and RHE. Electron paramagnetic resonance combined to spin-trapping in EpiSkin™ RHE confirmed the formation of C-radicals in the epidermal tissue from 10 mM ascaridole concentration, while reactivity studies toward amino acids showed electrophilic intermediates issued from radical rearrangements of ascaridole as the main reactive species. Activation of THP-1 cells, as surrogate for dendritic cells, that were cocultured with HaCaT was significantly upregulated after treatment with low micromolar concentrations based on cell surface expression of the co-stimulatory molecule CD86 and the adhesion molecule CD54. Placing THP-1 cells underneath the RHE allowed us to monitor which of the concentrations that produce radical(s) and/or protein antigens in the epidermal skin environment promote the activation of dendritic cells. We detected no significant upregulation of CD86/CD54 after topical RHE application of concentrations up to 30 mM ascaridole (t= 24 h) but clear upregulation after 60 mM.
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DOI：
10.1007/978-94-017-1607-9_3
发表时间：
1997
期刊：
Free radical research communications
影响因子：
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作者：
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DOI：
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发表时间：
1997
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DOI：
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发表时间：
2007-04-01
影响因子：
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Bocchietto, E.;Paolucci, C.;Burastero, S. E.
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DOI：
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发表时间：
2020
期刊：
La spectroscopie de résonance paramagnétique électronique
影响因子：
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