The activation of cultured keratinocytes by cholesterol depletion during reconstruction of a human epidermis is reminiscent of monolayer cultures

Évelyne De Vuyst, Séverine Giltaire, Catherine Lambert De Rouvroit, Aline Chrétien, Michel Salmon, Yves Poumay

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Abstract

Transient cholesterol depletion from plasma membranes of human keratinocytes has been shown to reversibly activate signalling pathways in monolayer cultures. Consecutive changes in gene expression have been characterized in such conditions and were interestingly found to be similar to transcriptional changes observed in keratinocytes of atopic dermatitis (AD) patients. As an inflammatory skin disease, AD notably results in altered histology of the epidermis associated with a defective epidermal barrier. To further investigate whether the activation of keratinocytes obtained by cholesterol depletion could be responsible for some epidermal alterations reported in AD, this study was undertaken to analyse cholesterol depletion in stratified cultures of keratinocytes, i.e. a reconstructed human epidermis (RHE). RHE contains heterogeneous populations of keratinocytes, either proliferating or progressively differentiating and stratifying towards the creation of a cornified barrier. Cholesterol depletion induced in this model was found reversible and resulted in activation of signalling pathways similar to those previously identified in monolayers. In addition, selected changes in the expression of several genes suggested that keratinocytes in RHE respond to cholesterol depletion as monolayers. However, preserved histology and barrier function indicate that some additional activation, likely from the immune system, is required to obtain epidermal alterations such as the ones found in AD.

Original languageEnglish
Pages (from-to)309-318
JournalArchives of Dermatological Research
Volume307
DOIs
Publication statusPublished - 15 Jan 2015

Keywords

  • Atopic dermatitis
  • Cell signalling
  • Cholesterol
  • Epidermal barrier
  • Methyl-beta-cyclodextrin
  • Reconstructed human epidermis

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