Methyl-β-cyclodextrin treatment combined to incubation with interleukin-4 reproduces major features of atopic dermatitis in a 3D-culture model.
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.
Research Unit for Molecular Physiology (URPhyM)-NARILIS, University of Namur, 61, rue de Bruxelles, B-5000, Namur, Belgium.|Skin Biology Laboratory, Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Tatiana
T
do Nascimento Pedrosa
Research Unit for Molecular Physiology (URPhyM)-NARILIS, University of Namur, 61, rue de Bruxelles, B-5000, Namur, Belgium.
Evelyne
E
De Vuyst
Research Unit for Molecular Physiology (URPhyM)-NARILIS, University of Namur, 61, rue de Bruxelles, B-5000, Namur, Belgium.
Abdallah
A
Mound
Research Unit for Molecular Physiology (URPhyM)-NARILIS, University of Namur, 61, rue de Bruxelles, B-5000, Namur, Belgium.
Catherine
C
Lambert de Rouvroit
Skin Biology Laboratory, Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Silvya Stuchi
SS
Maria-Engler
Research Unit for Molecular Physiology (URPhyM)-NARILIS, University of Namur, 61, rue de Bruxelles, B-5000, Namur, Belgium. yves.poumay@unamur.be.
Yves
http://orcid.org/0000-0001-5200-3367
Y
Poumay
D024402:Carbonic Anhydrase II / Q000235:genetics / Q000378:metabolism; D048430:Cell Shape; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017097:Electric Impedance; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000494:pharmacology*
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D047392:beta-Cyclodextrins; C064554:loricrin; C108732:methyl-beta-cyclodextrin; D015847:Interleukin-4; D024402:Carbonic Anhydrase II
Atopic dermatitis; Interleukin-4 and methyl-β-cyclodextrin; Reconstructed human epidermis