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.
Stefanato
Catherine M
CM
Section of Dermatopathology, Boston University School of Medicine, Boston, MA, USA. stefanat@bu.edu
Yaar
Mina
M
Bhawan
Jag
J
Phillips
Tania J
TJ
Kosmadaki
Maria G
MG
Botchkarev
Vladimir
V
Gilchrest
Barbara A
BA
D000328:Adult; D002452:Cell Count; D004817:Epidermis / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014466:Ultraviolet Rays
D007370:Interferon Type I; D011257:Pregnancy Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C020947:interferon tau; D020932:Nerve Growth Factor