22. Endothelins Control the Proliferation and Differentiation of Murine Melanocytes from UVB-induced Pigmented Spots

Tomohisa Hirobe

Keywords: melanocyte, keratinocyte, UVB, proliferation, differentiation

Long-term exposure to ultraviolet radiation B (UVB) is known to induce pigmented spots in the dorsal skin of hairless mice. By using a serum-free culture medium supplemented with dibutyryl adenosine 3':5'-cyclic monophosphate and basic fibroblast growth factor, it has been shown that the proliferation of epidermal melanoblasts and melanocytes from UVB-induced pigmented spots is greatly stimulated, and the stimulation is regulated by keratinocytes rather than melanocytes. In this study, we tried to understand what factors derived from keratinocytes were involved in regulating the proliferation and differentiation of epidermal melanoblasts and melanocytes from UVB-induced pigmented spots. For the purpose, antibodies towards growth factors and cytokines were added to the serum-free culture medium in the presence of keratinocytes. Results showed that antibodies towards endothelin (ET)-1, ET-2 and ET-3 inhibited the proliferation and differentiation of cultured epidermal melanoblasts/melanocytes from UVB-induced pigmented spots of hairless mice, but not from non-irradiated mice. In contrast, antibodies towards hepatocyte growth factor and leukemia growth factor failed to affect the proliferation and differentiation of cultured epidermal melanoblasts/melanocytes from both control and irradiated mice. These results suggest that ETs are keratinocyte-derived factors which are involved in regulating the proliferation and differentiation of epidermal melanoblasts/melanocytes from UVB-induced pigmented spots in the dorsal skin of hairless mice.

Publications:
Hirobe, T.: J. Invest. Dermatol. Symp. Proc., 6, 25-31, 2001.