On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis

Exp Dermatol. 2018 Dec;27(12):1403-1407. doi: 10.1111/exd.13810.

Abstract

Recent advances in the development of human-based in vitro models offer new tools for drug screening and mechanistic investigations of new therapeutic agents. However, there is a lack of evidence that disease models respond favourably to potential drug candidates. Atopic dermatitis (AD) is a very common disease associated with an altered skin barrier and chronic inflammation. Here, we demonstrate that the AD-like features of a reconstructed human epidermis (RHE) model treated with Th2 cytokines are reversed in the presence of molecules known to have a beneficial effect on damaged skin as a result of modulating various signalling cascades including the Liver X Receptors and JAK/STAT pathways. This work shows that standardized and reproducible RHE are relevant models for therapeutic research assessing new drug candidates aiming to restore epidermal integrity in an inflammatory environment.

Keywords: JAK/STAT; LXR; preclinical; skin model; therapeutic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / metabolism
  • Dermatitis, Atopic / drug therapy*
  • Drug Evaluation, Preclinical
  • Epidermal Cells
  • Epidermis / drug effects*
  • Homeostasis
  • Humans
  • Immune System
  • In Vitro Techniques
  • Inflammation
  • Keratinocytes / metabolism
  • Liver X Receptors / metabolism
  • Models, Anatomic
  • Phenotype
  • Signal Transduction
  • Skin / drug effects*
  • Skin / pathology
  • Th2 Cells / cytology

Substances

  • Cytokines
  • Liver X Receptors