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首页> 外文期刊>Archives of dermatological research. >Methyl-beta-cyclodextrin treatment combined to incubation with interleukin-4 reproduces major features of atopic dermatitis in a 3D-culture model
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Methyl-beta-cyclodextrin treatment combined to incubation with interleukin-4 reproduces major features of atopic dermatitis in a 3D-culture model

机译：与白细胞介素-4孵育的甲基β-环糊精治疗在3D培养模型中再现特应性皮炎的主要特征

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摘要

Atopic dermatitis (AD) skin is characterized by over-expression of interleukin (IL)-4, IL-13 and IL-25. When methyl-beta-cyclodextrin (M beta CD) treatment preceded exposure to these interleukins, combination of both treatments was found to mimic hallmarks of AD in vitro, such as barrier weakening, histological alterations and typical signaling responses in a reconstructed human epidermis (RHE). However, the respective role of each IL and whether any of them is critical when combined with M beta CD treatment was unknown. Therefore, this work aimed to distinguish RHE responses after exposure to M beta CD and each one of the three IL reported to mimic typical features of AD. IL-4 incubation preceded by M beta CD was found responsible for altered histology, as well as for barrier alterations, evidenced by electrical resistance and dye permeation measurements. This combination further decreased loricrin (LOR) immunoreactivity, whereas mainly IL-25, combined to M beta CD treatment, was able to downregulate filaggrin (FLG) mRNA level. Carbonic anhydrase II (CA2) and hyaluronan synthase 3 (HAS3), two other markers up-regulated in AD, were also induced when M beta CD treatment was followed by IL-4, whilst the expression of neural epidermal growth factor-like 2 (NELL2) was up-regulated by paired IL-4 and IL-13. In conclusion, multiple features of AD were found in this in vitro model mainly when treatment of RHE by IL-4 was conducted after preliminary M beta CD incubation.
机译：特征性皮炎（AD）皮肤的特征是白细胞介素（IL）-4，IL-13和IL-25的过表达。当甲基 - β-环糊精（MβCD）治疗之前暴露于这些白细胞介环时，发现两种治疗的组合在体外模仿AD的标志，例如屏障弱化，组织学改变和重建的人表皮中的典型信号响应（RHE ）。然而，当与MβCD处理结合未知时，每个IL的各自的作用以及它们是否至关重要。因此，这项工作旨在将RHE反应区分在暴露于MβCD后，并且据报道的三个IL中的每一个用于模仿广告的典型特征。发现IL-4之前的培养是诱导改变的组织学，以及通过电阻和染料渗透测量证明的阻隔改变。这种组合进一步降低了鲁兰林（LOR）免疫反应性，而主要是IL-25组合到MβCD处理，能够下调Fileagrin（FLG）mRNA水平。碳酸酐酶II（CA2）和透明质酸合酶3（HAS3），当MβCD处理之后，也诱导了在AD中上调的另外两个上调的标记，同时是IL-4的，同时神经表皮生长因子样2（ Nell2）由配对的IL-4和IL-13上调。总之，在初步MβCD孵育后，在该体外模型中发现了许多特征，主要是IL-4的rhe治疗。

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