USE OF EPIDERM™ AS AN INFLAMMATORY MODEL FOR PRE-CLINICAL SCREENING.

Organotypic skin models are becoming widely used by the pharmaceutical and cosmetics industries as an alternative to animal testing for screening cosmetics and potential therapeutics for safety and efficacy. The purpose of this study was to test if MatTek’s EpiDerm organotypic skin model can be induced at the molecular level to initiate an inflammatory response. EpiDerm is a highly differentiated, three-dimensional epidermal tissue composed of normal human keratinocytes. Keratinocytes are known to be involved with the progression of numerous inflammatory skin diseases such as psoriasis and contact dermatitis. Molecular markers of these skin diseases include intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and interleukin 20 (IL-20). In the present work, EpiDerm tissues were treated with a panel of cytokines including IFN-ã, IL-1á, IL-1â, TNFá, and various combinations thereof. ICAM-1, iNOS and IL-20 message levels of the tissues were examined by RT-PCR. IL-20 message levels were significantly up-regulated by treatment with some of these cytokines. Inducible nitric oxide synthase was also up-regulated. However, there were temporal differences in response between the two genes. ICAM-1 levels were also enhanced following cytokine treatment and detectable soluble ICAM levels were present in the supernatant, as analyzed by ELISA. In conclusion, this study shows that genes important in inflammatory skin response can be regulated in EpiDerm tissues by the various cytokines studied. Furthermore, these results suggest that EpiDerm can be used as in vitro skin model for testing therapeutics that target suppression or inhibition of inflammatory responses in epidermis.

Contact Dermatitis, EpiDerm, ICAM-1, IFN-gamma, IL-1a, IL-1b, IL-20, INOS (iNOS, inos), Inducible nitric oxide synthase (iNOS), Inflammation, Inflammatory, Inflammatory response, Pre-clinical screening, Psoriasis, TNF-a