Modulations of nerve growth factor and Bcl-2 in ultraviolet-irradiated human epidermis

Background: Ultraviolet (UV) irradiation to the skin causes apoptosis of keratinocytes. Melanocytes are more resistant to UV-induced apoptosis, due, in part, to high levels of antiapoptotic proteins such as Bcl-2. In vitro studies have shown that nerve growth factor (NGF), a neurotrophic polypeptide, is produced by keratinocytes and exerts a protective role for melanocytes by upregulating Bcl-2. The purpose of this study was to determine NGF and Bcl-2 modulations in UV-irradiated human skin. Methods: Nine volunteers were irradiated with two minimal erythema doses using solar-simulated UV irradiation. Seventy-two hours post irradiation, skin biopsies were obtained from irradiated and sun-protected skin. The skin specimens were stained with anti-tyrosinase-related protein-1 monoclonal antibody IgG2a (Mel-5), anti-Bcl-2 (monoclonal antibody IgG-kappa), and with anti-NGF (polyclonal antibody IgG). Results: NGF staining was identified within the cytoplasm of epidermal melanocytes, similar to the staining observed for TRP-1 and Bcl-2. While no significant difference in the number of TRP-1- and Bcl-2-positive melanocytes was observed between irradiated and non-irradiated skin within 72 h, the number of NGF-positive melanocytes decreased significantly, 72 h after UV irradiation (p < 0.024). NGF was also identified within keratinocytes, and while non-irradiated skin exhibited cytoplasmic NGF staining throughout the epidermis, NGF staining was reduced in the lower epidermal layers after UV irradiation. Conclusions: This is the first in vivo study showing NGF to be present in melanocytes, as well as showing modulations of NGF and Bcl-2 in melanocytes, following solar-simulated UV irradiation.