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

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Abstract

Atopic dermatitis (AD) skin is characterized by over-expression of interleukin (IL)-4, IL-13 and IL-25. When methyl-β-cyclodextrin (MβCD) 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 MβCD treatment was unknown. Therefore, this work aimed to distinguish RHE responses after exposure to MβCD and each one of the three IL reported to mimic typical features of AD. IL-4 incubation preceded by MβCD 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 MβCD 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 MβCD 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 MβCD incubation.

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Acknowledgements

The authors gratefully thank B. Balau, V. De Glas and D. Van Vlaender for providing technical help. Special thanks are addressed to Dr. B. Bienfait (Clinique St. Luc, Namur-Bouge, Belgium) for providing skin samples.

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Authors and Affiliations

  1. Research Unit for Molecular Physiology (URPhyM)-NARILIS, University of Namur, 61, rue de Bruxelles, B-5000, Namur, Belgium

    Tatiana do Nascimento Pedrosa, Evelyne De Vuyst, Abdallah Mound, Catherine Lambert de Rouvroit & Yves Poumay

  2. Skin Biology Laboratory, Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

    Tatiana do Nascimento Pedrosa & Silvya Stuchi Maria-Engler

Authors
  1. Tatiana do Nascimento Pedrosa
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  2. Evelyne De Vuyst
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  6. Yves Poumay
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Correspondence to Yves Poumay.

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The authors state no conflict of interest. This study was conducted according to the Declaration of Helsinki Principles and approved by the Ethics Committees. Financial support was provided by FRFC 2.4.522.10F Grant to YP and FAPESP (Grant # 2015/23938-0) to TDNP.

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do Nascimento Pedrosa, T., De Vuyst, E., Mound, A. et al. Methyl-β-cyclodextrin treatment combined to incubation with interleukin-4 reproduces major features of atopic dermatitis in a 3D-culture model. Arch Dermatol Res 309, 63–69 (2017). https://doi.org/10.1007/s00403-016-1699-7

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  • DOI: https://doi.org/10.1007/s00403-016-1699-7

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