We previously reported that increased expression of the
endothelin (EDN)1/EDNB receptor (EDNBR) as well as the
stem cell factor (SCF)/
SCF receptor (c-KIT) linkages is mainly responsible for the activation of melanocytes in the epidermal
hyperpigmentation of ultraviolet (UV)-B
melanosis and
lentigo senilis (LS). In this study, we characterized
seborrheic keratosis (SK) to examine the paracrine
cytokine mechanism(s) involved in its epidermal
hyperpigmentation by reverse transcription polymerase chain reaction, immunohistochemistry and western blotting analyses. In contrast to our previous study which showed the upregulated expression of EDN1 and EDNBR at the transcriptional and translational levels in the epidermis of SK, we observed unexpectedly that the
cytokine SCF and its receptor c-KIT are not upregulated, but are downregulated at both the gene and
protein levels. We established SK cell lines to examine whether SK basaloid cells are less sensitive to SCF-inducible stimulation than are normal human keratinocytes (NHK). Comparison of the stimulatory effects of
interleukin (IL)-1α or
tumor necrosis factor (TNF)-α on SCF production between SK cells and NHK demonstrated that SK cells do not respond to IL-1α or TNF-α to stimulate production of SCF, whereas a significant stimulation of SCF is elicited by those same
cytokines in NHK. These finding underscore a role of phenotypic changes in melanogenic
cytokine production in the epidermis between SK and LS/UV-B
melanosis.