CYTOKINE RESPONSE OF THE EPIDERM SKIN MODEL TO TOPICALLY APPLIED IRRITANTS AND TOXICANTS.
EpiDerm™, MatTek Corporation’s in vitro reproduction of the human epidermis provides a convenient way in which toxicity and irritation potential of chemicals and physical stresses can be assessed. Derived from single strains of human keratinocytes, the model contains layers of cells which have differentiated into easily recognizable component strata of human epidermis. These include basal, spinous and granular layers and very importantly, a cornified later which conveys to the model a barrier function which gives water flux of the same order of magnitude as seen with human epidermis. This allows studies to be done in which chemical and physical agents are applied to and interact with a surface which closely approximates that of skin in both architecture and properties. Contact dermatitis is a clinical condition produced by skin contact with irritants, allergens, electromagnetic radiation, or photoallergens and ultraviolet light, and is a consequence, at least in part, of the interaction between these agents and individual epidermis. Contact irritants and allergens ranging in severity from to harsh were applied to EpiDerm and changes induced in the model were observed. Damage was assessed by histologic examination and degree of viability was measured using the MTT reaction. In addition, release of cytokines and proinflammatory mediators usually associated with irritancy such as IL-1α and prostaglandin E2 (PGE-2), were determined using ELISA techniques. With most test materials, maximal amounts of IL-1α and PGE-2 were released after substantial decreases in cell viability and histological damage occurred. However, several tests agents induced significant release at levels which produced little or no cytotoxicity. In addition, a correlation was evident between irritant severity and dose size required to produce changes in EpiDerm. These observations demonstrated the utility of EpiDerm in modeling some aspects of contact irritancy and suggest a predictive value for the assessment of irritant severity.
Allergens, Barrier properties formation, Chemical irritants/irritancy assessment, Chemicals, Contact dermatitis, Cutaneous irritancy, Cutaneous irritation, Cutaneous toxicity, Cytokines, Cytotoxicity, Dermal, Dermal irritancy, Dermal irritancy testing, Dermal irritation, EpiDerm, MTT, MTT ET-50 tissue viability assay, MTT assay, PGE-2, Photoallergens, Phototoxicity, Prostaglandin E-2, Skin irritancy, Skin irritation, Sun screens, UVA, UVB, Viability
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