320 Development of a 3D model mimicking atopic dermatitis for the design of new therapeutic molecules

Abstract

Acne vulgaris is a disease of pilosebaceous units associated with increased follicular stratum corneum (SC) thickness and hyperkeratinization, increased sebum secretion, inflammation and impaired skin barrier. We hypothesized that excess unsaturated free fatty acids (UFFAs) in sebum may contribute to these symptoms seen in Acne. Therefore, skin surface lipids in acne and healthy subjects were investigated. In addition, a human epidermal equivalent (HEE) model treated topically with an UFFA was developed mimicking these symptoms seen in Acne. Gene expression profiling of human skin biopsies with and without acne lesions as well as of UFFA-treated HEEs Vs. controls was also performed. Increased levels of UFFAs were observed in skin lipids of human acne subjects. Topical treatment of HEEs with an UFFA resulted in impaired barrier and increased secretion of interleukin-1a (IL-1a), associated with SC thickening and hyperkeratinization, and with increased SC lipid conformational disorder indicating a decrease in barrier integrity. Furthermore, gene expression analysis showed a similar increase in gene expression of inflammatory cytokines and epidermal differentiation both in acne lesions and UFFA-treated HEEs. These data are in agreement with the hypothesis that excess unsaturated free fatty acids (UFFAs) in sebum may contribute to the increased follicular stratum corneum (SC) thickness and hyperkeratinization, inflammation and impaired skin barrier seen in Acne. Taken together, these results suggest that UFFA-treated epidermal tissue induces a phenotypic in vitro model of acne hyperkeratinization which can be useful for the investigation of treatments that modulate acne.