Augmentation of the contact allergen-mediated sensitization in Mdr1-/-, Mrp1-/-, Mrp5-/-, Itih5-/- and Itih5-/-/Mrp5-/- mouse models as well as in murine and human 3D skin models

在 Mdr1-/-、Mrp1-/-、Mrp5-/-、Itih5-/- 和 Itih5-/-/Mrp5-/- 小鼠模型以及小鼠和人类 3D 皮肤模型中增强接触过敏原介导的致敏作用

• 批准号: 335120387
• 负责人: Professor Dr. Jens Malte Baron
• 金额: --
• 依托单位: Klinik für Dermatologie und Allergologie - Hautklinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/335120387?language=en
• 关键词: Augmentation; contact; allergen; mediated; sensitization

In daily life, combined skin exposure to contact allergens and irritants is very common. Recent studies provide evidence that irritants augment the development of allergic contact dermatitis, especially against weak sensitizing substances. Previous studies to this project showed an important role of multidrug resistance related proteins (MRPs) MDR1, MRP1 and MRP5 as well as ITI heavy chain 5 (ITIH5) in the pathogenesis of allergic contact dermatitis. It was shown that MRPs function as transporters of contact allergens and hyaluronan. Irritants can regulate the expression of the transport proteins in skin cells through the release of cytokines. In addition, it has been demonstrated that ITIH5 that interacts with hyaluronan plays an important role in delayed type hypersensitivity responses of the skin. Therefore, we want to study the effect of topically applied contact allergens (eugenol and methylisothiazolinone) without or in combination with substances that could increase augmentation effects (sodium lauryl sulfat, hyaluronan and diethylhexyl phthalate) in Mdr1-/-, Mrp1-/-, Mrp5-/-, Itih5-/- and Itih5-/-/Mrp5-/- knockout mouse models, organotypic murine 3D skin models and HaCat based knockdown transfectants employing immunohistologic- and microarray analyses.From these studies we anticipate further insight in the complex interaction of skin irritants and contact allergens in the pathogenesis of eczematous delayed type hypersensitivity responses of the human skin and the establishment of test systems to visualize augmentation effects.

在日常生活中，皮肤接触过敏原和刺激物是很常见的。最近的研究提供证据表明，刺激物增加了过敏性接触性皮炎的发展，特别是对弱致敏物质。本项目前期研究表明，多药耐药相关蛋白（MRPs） MDR1、MRP1、MRP5以及ITI重链5 （ITIH5）在变应性接触性皮炎发病机制中的重要作用。研究表明，MRPs作为接触性过敏原和透明质酸的转运体。刺激物可以通过释放细胞因子调节皮肤细胞中转运蛋白的表达。此外，已经证明ITIH5与透明质酸相互作用在皮肤延迟型超敏反应中起重要作用。因此，我们希望通过免疫组织和微阵列分析研究局部应用接触性过敏原（丁香酚和甲基异噻唑啉酮）对Mdr1-/-、Mrp1-/-、Mrp5-/-、Itih5-/-和Itih5-/-/Mrp5-/-敲除小鼠模型、器官型小鼠3D皮肤模型和基于HaCat敲除的转染物的影响，这些物质可以增加增强效应（月桂基磺酸钠、透明质酸和邻苯二甲酸二乙基己基）。从这些研究中，我们期望进一步了解皮肤刺激物和接触过敏原在人类皮肤湿疹延迟型超敏反应发病机制中的复杂相互作用，并建立测试系统来可视化增强效应。

项目成果

Inter-α-Trypsin Inhibitor Heavy Chain 5 (ITIH5) Is a Natural Stabilizer of Hyaluronan That Modulates Biological Processes in the Skin

• DOI: 10.1159/000509371
• 发表时间: 2020-10-01
• 期刊: SKIN PHARMACOLOGY AND PHYSIOLOGY
• 影响因子: 2.7
• 作者: Huth, Sebastian;Huth, Laura;Baron, Jens Malte
• 通讯作者: Baron, Jens Malte