Differential effects of ceramide on cell viability and extracellular matrix remodeling in keratinocytes and fibroblasts.

Ceramides are used in skin care and treatment of dermatological diseases. Cell viability and extracellular matrix (ECM) remodeling are important parameters in skin health. Skin photoaging, from exposure to ultraviolet radiation, is associated with epidermal hyperplasia and dermal ECM atrophy caused by alterations in expression of matrixmetalloproteinases (MMPs), elastin and transforming growth factor-beta (TGF-beta). The purpose of this study was to determine the effects of c2-ceramide (ceramide) on the cell viability and expression of TGF-beta, MMP-1 and elastin in cultured keratinocytes and fibroblasts. Ceramide inhibited keratinocyte cell viability by apoptosis and stimulated expression of elastin, MMP-1 and TGF-beta, suggesting improved epidermal functioning by a TGF-beta mechanism. Conversely, ceramide stimulated fibroblast cell growth at the lower concentrations and inhibited the expression of MMP-1, elastin and TGF-beta, which indicates a predominantly beneficial effect in the prevention of photoaging-associated dermal alterationby TGF-beta and non-TGF-beta mechanisms. The regulation of MMP-1 expression by ceramide was transcriptionally mediated and via the activator protein-1 sequence in both keratinocytes and fibroblasts. The study delineates the specific, though differential, beneficial effects of ceramide in the prevention of epidermal hyperplasia and dermal ECM remodeling, associated with photoaging.