Biphasic Expression of Two Paracrine Melanogenic Cytokines, Stem Cell Factor and Endothelin-1, in Ultraviolet B-Induced Human Melanogenesis

Abstract

Stem cell factor (SCF) and endothelin-1 (ET-1) have been reported to be up-regulated at the protein and gene levels in human epidermis after ultraviolet B (UVB) irradiation and to play central roles in UVBinduced pigmentation. However, little is known about the time sequence of SCF and ET-1 expression in UVB-exposed human epidermis and the coordination of their roles during epidermal pigmentation. To clarify such parameters in UVB-exposed human skin, we measured the expression patterns of SCF and ET-1 (as well as of their corresponding receptors) at the gene level at various times during UVB-induced human pigmentation. When human forearm skin was exposed to UVB radiation at two minimal erythemal doses, the expression of SCF mRNA transcripts was significantly enhanced at 3 days after irradiation with an early decrease and subsequently constant expression of SCF receptor (c-KIT) mRNA transcripts. In contrast, up-regulation of ET-1 and endothelin B receptor (ET B R) mRNA expression was synchronized at 5 to 10 days after irradiation in concert with an increased expression of tyrosinase mRNA transcripts and the increase in pigmentation. In parallel the expression of tyrosinase and ET B R proteins as well as ET-1 was up-regulated at 7 to 10 days after irradiation, whereas KIT protein decreased at 3 days after irradiation and returned to the nonirradiated control level at 5 days after irradiation. When cultured human melanocytes were treated with human recombinant SCF, ET B R protein expression and the binding of 125 I-labeled ET-1 to the ET B R were significantly increased, further suggesting the preferential and coordinated role of early expression of SCF in UVB-induced melanogenesis. These findings suggest that SCF/KIT signaling is predominantly involved in the early phase of UVB-induced human pigmentation during which it stimulates the ET-1/ET B R linkage that is associated with the later phase of UVB-induced melanogenesis.

Inhibition of melanogenesis by Gaillardia aristata flower extract

“…The mechanism of epidermal hyper-pigmentation occurs by the increased expression level of ET-1 and SCF, or the decreased expression of TNF-α and IL-6. In particular, SCF and ET-1 are germane to the hyper-pigmentary mechanism by UVB-induced melanin synthesis [26][27][28][29][30]. Presently, GAE inhibited SCF-stimulated pigmentation in human epidermal equivalents.…”

Mechanistic Effects of Long-Term Ultraviolet B Irradiation Induce Epidermal and Dermal Changes in Human Skin Xenografts

“…Subsequent visualization was performed and normalized against a control protein, ␤-actin (Sigma) as described elsewhere. 59 …”

UV-B Radiation Induces Macrophage Migration Inhibitory Factor–Mediated Melanogenesis through Activation of Protease-Activated Receptor-2 and Stem Cell Factor in Keratinocytes

“…5 In addition, prostaglandins (PGs) are key mediators of diverse functions in the skin; and several reports 6,7 have suggested that PGs mediate postinflammatory pigmentary changes by modulating melanin synthesis and melanocyte dendricity.…”

“…[2][3][4] The two main paracrine melanogenic cytokines, stem cell factor (SCF) and endothelin (ET)-1, have been demonstrated to play pivotal roles in skin pigmentation, including UV-Binduced pigmentation. 5 In addition, prostaglandins (PGs) are key mediators of diverse functions in the skin; and several reports 6,7 have suggested that PGs mediate postinflammatory pigmentary changes by modulating melanin synthesis and melanocyte dendricity.…”

“…4 The production and secretion of SCF and ET-1 by keratinocytes are generally augmented by several cytokines, such as IL-1␣ and tumor necrosis factor (TNF)-␣. 5 The exogenous addition of TNF-␣ to human keratinocytes in culture stimulates the secretion of ET-1 because of increased transcription. 11 The cytokine macrophage migration inhibitory factor (MIF) was first discovered 50 years ago as a T-cellderived factor that inhibits the random migration of macrophages.…”