title: From the morphological to the transcriptomic characterization of a compromised three-dimensional in vitro model mimicking atopic dermatitis.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a chronic inflammatory skin disease in which skin barrier function is disrupted. In this AD environment, proinflammatory cytokines are upregulated, promoting a vicious circle of inflammation. Although several three-dimensional in vitro models mimicking AD have been published, no study has presented a fully characterized and controlled model of AD-related inflammation.
  
  
  OBJECTIVE
  To develop and characterize, from the morphological to the molecular level, a compromised reconstructed epidermis (RE) mimicking AD-related inflammation in vitro.
  
  
  METHODS
  Normal human keratinocytes were used to generate RE, treated or not with an inflammatory cocktail (polyinosinic-polycytidylic acid, tumour necrosis factor-α, interleukin-4 and interleukin-13).
  
  
  RESULTS
  The inflammatory cocktail induces some modifications observed in patients with AD: (i) it leads to spongiosis; (ii) it alters early and terminal differentiation proteins; (iii) it increases thymic stromal lymphopoietin and interleukin-8 secretion by keratinocytes and (iv) it results in a specific gene expression pattern.
  
  
  CONCLUSIONS
  The inflammatory context contributes to the morphological, functional and transcriptomic changes observed in AD skin. As a result, this compromised RE model shares some characteristics with those found in AD skin and thus can be used as a relevant tool for screening formulations and drugs for the treatment of AD.
authors.affiliation: R&D Department, SILAB, BP 213, 19108, Brive CEDEX, France.
authors.forename: P
authors.initials: P
authors.lastname: Rouaud-Tinguely
authors.affiliation: R&D Department, SILAB, BP 213, 19108, Brive CEDEX, France.
authors.forename: D
authors.initials: D
authors.lastname: Boudier
authors.affiliation: R&D Department, SILAB, BP 213, 19108, Brive CEDEX, France.
authors.forename: L
authors.initials: L
authors.lastname: Marchand
authors.affiliation: R&D Department, SILAB, BP 213, 19108, Brive CEDEX, France.
authors.forename: V
authors.initials: V
authors.lastname: Barruche
authors.affiliation: R&D Department, SILAB, BP 213, 19108, Brive CEDEX, France.
authors.forename: S
authors.initials: S
authors.lastname: Bordes
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Inserm U1043, CNRS U5282, Université de Toulouse, Toulouse, France.
authors.forename: H
authors.initials: H
authors.lastname: Coppin
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Inserm U1043, CNRS U5282, Université de Toulouse, Toulouse, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Roth
authors.affiliation: R&D Department, SILAB, BP 213, 19108, Brive CEDEX, France.
authors.forename: B
authors.initials: B
authors.lastname: Closs
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics / Q000473:pathology*; D004338:Drug Combinations; D004817:Epidermis / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D018793:Interleukin-13; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D011070:Poly I-C