title: Paracrine cytokine mechanisms underlying the hyperpigmentation of seborrheic keratosis in covered skin areas.
abstract: 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.
authors.affiliation: Department of Dermatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takenaka
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Hayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawashima
authors.forename: Genji
authors.initials: G
authors.lastname: Imokawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D015536:Down-Regulation; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D006801:Humans; D017495:Hyperpigmentation / Q000378:metabolism*; D007150:Immunohistochemistry; D017492:Keratosis, Seborrheic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019899:Paracrine Communication; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D019089:Stem Cell Factor / Q000378:metabolism*; D015854:Up-Regulation; D000521:alpha-MSH / Q000276:immunology / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D019089:Stem Cell Factor; D000521:alpha-MSH; D019009:Proto-Oncogene Proteins c-kit
keywords: endothelin-1; lentigo senilis; seborrheic keratosis; stem cell factor