NITRIC-OXIDE PRODUCED BY ULTRAVIOLET-IRRADIATED KERATINOCYTES STIMULATES MELANOGENESIS

Ultraviolet (UV) radiation is the main physiological stimulus for huma n skin pigmentation. Within the epidermal-melanin unit, melanocytes sy nthesize and transfer melanin to the surrounding keratinocytes. Kerati nocytes produce paracrine factors that affect melanocyte proliferation , dendricity, and melanin synthesis. In this report, we show that norm al human keratinocytes secrete nitric oxide (NO) in response to UVA an d UVB radiation, and we demonstrate that the constitutive isoform of k eratinocyte NO synthase is involved in this process. Next, we investig ate the melanogenic effect of NO produced by keratinocytes in response to UV radiation using melanocyte and keratinocyte cocultures. Conditi oned media from UV-exposed keratinocytes stimulate tyrosinase activity of melanocytes. This effect is reversed by NO scavengers, suggesting an important role for NO in UV-induced melanogenesis. Moreover, melano cytes respond to NO-donors by decreased growth, enhanced dendricity, a nd melanogenesis. The rise in melanogenesis induced by NO-generating c ompounds is associated with an increased amount of both tyrosinase and tyrosinase-related protein 1. These observations suggest that NO play s an important role in the paracrine mediation of UV-induced melanogen esis.