1. ¹Skin Sciences Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
2. ²Kao Biological Science Laboratories, Haga, Tochigi, Japan
3. ³Department of Dermatology, Tokyo Medical University, Tokyo, Japan
4. ⁴Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Correspondence: Dr RE Boissy, PhD, Department of Dermatology, University of Cincinnati College of Medicine, 231 Albert Sabin Way ML-0592, Cincinnati, OH 45267-0592, USA. E-mail: boissyre@ucmail.uc.edu

^*These authors contributed equally to this work.

Received 17 March 2006; Accepted 11 July 2006; Published online 28 August 2006.

Abstract

The two paracrine melanogenic cytokines, stem cell factor (SCF) and endothelin-1 (ET-1), have been demonstrated to play pivotal roles in skin pigmentation including UVB-induced pigmentation and senile lentigo. However, little is known regarding their interactive effect on skin pigmentation. In order to investigate their roles in vivo, facultative pigmentation of human skin xenografts on severe combined immunodeficient (SCID) mice was assessed. After 1 week of acclimation in a pathogen-free barrier, dermatomed fresh cadaveric skin was surgically grafted onto the back of the mice and allowed to heal for 5–6 weeks prior to cytokine administration. Intradermal injections of SCF at 0.7 or 2.0 g significantly increased skin pigmentation when compared to vehicle control. Despite the lack of a dose-dependent pigmentation response following ET-1 administration, the combination of 0.2 g SCF and 0.1 g ET-1 demonstrated a statistically significant increase in tyrosinase gene expression substantiated by the enhancement of melanin content and skin pigmentation compared to treatment with SCF alone or ET-1 alone. These findings establish an in vivo interaction between SCF and ET-1 with regard to their capacity to effect an increase in skin pigmentation.