Methyl-beta-cyclodextrin treatment combined to incubation with interleukin-4 reproduces major features of atopic dermatitis in a 3D-culture model

作者：Pedrosa Tatiana do Nascimento; De Vuyst Evelyne; Mound Abdallah; de Rouvroit Catherine Lambert; Maria Engler Silvya Stuchi; Poumay Yves^*

来源：Archives of Dermatological Research, 2017, 309(1): 63-69.

DOI：10.1007/s00403-016-1699-7

• Reconstructed human epidermis
• Atopic dermatitis
• Interleukin-4 and methyl-beta-cyclodextrin

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.

• 出版日期2017-1