ABSTRACT
Psoriasis is a chronic inflammatory skin disease for which no cure has emerged. Its complex etiology requires the development of an in vitro model representative of the pathology. In this study, we exploited gene profiling analyses on microarray in order to characterize and further optimize the production of a human psoriatic skin model representative of this in vivo skin disease. Various skin substitutes were produced by tissue-engineering using biopsies from normal, healthy donors, or from lesional or non-lesional skin samples from patients with psoriasis, and their gene expression profiles were examined by DNA microarray. We demonstrated that more than 3540 and 1088 genes (two-fold change) were deregulated between healthy/lesional and lesional/non-lesional psoriatic substitutes, respectively. Moreover, several genes related to lipid metabolism, such as PLA2G4E and PLA2G4C, were identified as repressed in the lesional substitutes. In conclusion, gene profiling analyses identified a list of deregulated candidate genes associated with various metabolic pathways that may contribute to the progression of psoriasis.
Subject(s)
Gene Expression Profiling/methods , Psoriasis/genetics , Skin, Artificial , Skin/metabolism , Tissue Engineering/methods , Adolescent , Adult , Aged , Cells, Cultured , Cytokines/genetics , Gene Ontology , Humans , Intercellular Signaling Peptides and Proteins/genetics , Middle Aged , Skin/pathology , Young AdultABSTRACT
AIM: Psoriasis is a chronic inflammatory skin disease. To study its complex etiology, a psoriatic skin substitute model supplemented with a cytokine cocktail has been used. MATERIALS & METHODS: Reconstructed psoriatic skin substitutes were supplemented with a cocktail of four cytokines: TNF-α, IL-1α, IL-6 and IL-17A, to monitor their impact on gene expression by DNA microarray. RESULTS: Gene profiling analyses identified several deregulated genes reported as being also deregulated in psoriasis skin in vivo (S100A12, IL-8, DEFB4A and KYNU). The expression of those genes was dramatically increased compared with basal levels of controls (p < 0.005 to < 0.05). CONCLUSION: Psoriatic substitutes supplemented with a cocktail of TNF-α, IL-1α, IL-6 and IL-17A showed similar transcriptome alterations to those found in psoriasis.
