The paracrine role of stem cell factor/c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation

The interaction of stem cell factor with its receptor, c-kit, is well known to be critical to the survival of melanocytes, Little is known about the r ole(s) of the stem cell factor/c-kit interaction in epidermal pigmentation, however. To clarify whether the stem cell factor/c-kit signaling has a par acrine role in ultraviolet-B-induced pigmentation, we determined whether th e exposure of human keratinocytes, melanocytes, and the epidermis to ultrav iolet B light stimulates the expression of stem cell factor or c-kit at the gene and/or protein levels, We further examined whether interrupting the b inding of stem cell factor to c-kit by subepidermal injection of a monoclon al antibody to c-kit affects ultraviolet-B-induced pigmentation in brownish guinea pig skin. When human keratinocytes and melanocytes in culture were exposed to ultraviolet B light, transcripts of stem cell factor and c-kit l as assessed by reverse transcription polymerase chain reaction) and express ion of those proteins (by enzyme-linked immunosorbent assay and western blo tting) increased significantly and peaked at a dose of 20-40 mJ per cm(2). In ultraviolet-B-exposed human epidermis, stem cell factor transcripts and protein expression were also markedly enhanced compared with the nonexposed epidermis. Immunohistochemistry with antibodies to stem cell factor reveal ed an increased staining in the ultraviolet-B-exposed epidermis, which was accompanied by a slight epidermal hyperplasia, In the course of ultraviolet -B-induced pigmentation of brownish guinea pig skin, the subepidermal injec tion of c-kit inhibitory antibodies completely abolished the induction of p igmentation in the ultraviolet-B-exposed area, and there was no increase in the numb er of dihydroxyphenylalanine-positive melanocytes, These findings indicate that the stem cell factor/c-kit signaling is critically involved in the biologic mechanism of ultraviolet-B-induced pigmentation.