Less Keratinocyte-Derived Factors Related to More Keratinocyte Apoptosis in Depigmented than Normally Pigmented Suction-Blistered Epidermis May Cause Passive Melanocyte Death in Vitiligo

Abstract

Stem cell factor (SCF) of keratinocyte origin regulates melanocyte growth and survival. Deprivation of survival factors causes the apoptosis of melanocytes. Vitiligo often develops following physical trauma, even if this is minor. The exact mechanism of the Koebner phenomenon in vitiligo is unclear. Apoptosis of keratinocytes, which occurs more in depigmented suction-blistered epidermis than in the normally pigmented counterpart, could reduce levels of keratinocyte-derived factors such as SCF and basic fibroblast growth factor (bFGF). Levels of SCF expression were examined in the depigmented and normally pigmented paired epidermis of 19 patients with vitiligo, and bFGF expression in six patients. The expression of SCF (p<0.001) and bFGF was usually reduced in the depigmented compared with the normally pigmented epidermis. Apoptosis of cultured normal human keratinocytes, which was induced by staurosporine, resulted in a concentration-dependent decrease in levels of SCF mRNA and protein. Normal human melanocytes proliferated more in medium containing SCF or keratinocyte (XB-2) feeder than in medium with neither. Deprivation of SCF or keratinocyte feeder in the culture medium induced a marked decrease in melanocytes as a result of apoptosis. Therefore, lower expression of keratinocyte-derived factors, including SCF, in vitiliginous keratinocytes, which could result from keratinocyte apoptosis, might be responsible for passive melanocyte death and may explain the Koebner phenomenon.

Decreased CD117 expression in hypopigmented mycosis fungoides correlates with hypomelanosis: lessons learned from vitiligo

“…[13][14][15][16][17][18][19][20] The survival and growth of melanocytes is regulated by binding of stem cell factor (SCF) produced by keratinocytes, to its receptor CD117 on the surface of melanocytes. 20 Melanocyte-specific microphthalmia-associated transcription factor (MITF-M) expression is regulated downstream of the SCF/SCF receptor linkage 21 and serves as a transcription factor controlling the expression of tyrosinase mRNA, which essentially leads to melanocyte differentiation. 22 It is known that CD117 and MITF-M show complex interactions; CD117 signaling modulates MITF-M activity and stability in melanocytes, and MITF-M in turn is needed for the maintenance of CD117 expression on melanoblasts.…”

“…[13][14][15][16][17][18][19][20] Experimental data support the role of T-cells within active inflammatory lesions of vitiligo in initiating apoptosis of melanocytes. [13][14][15] Abnormal interactions between melanocytes and surrounding keratinocytes resulting from a decrease in the melanogenic cytokines produced by the keratinocytes, or from downregulation of specific receptors on the surface of melanocytes have been considered as possible pathways in pathogenesis of hypopigmentation in vitiligo.…”

“…[13][14][15] Abnormal interactions between melanocytes and surrounding keratinocytes resulting from a decrease in the melanogenic cytokines produced by the keratinocytes, or from downregulation of specific receptors on the surface of melanocytes have been considered as possible pathways in pathogenesis of hypopigmentation in vitiligo. 19,20 We hypothesized that as in vitiligo, the pigment loss in hypopigmented mycosis fungoides may be related to alterations in expression of CD117 (also known as stem cell factor receptor or c-KIT), which is present on epidermal melanocytes. To test this hypothesis, we analyzed skin specimens of hypopigmented mycosis fungoides and vitiligo immunohistochemically for CD117 and pan-melanoma antigen cocktail (gp100, tyrosinase, and MART-1) expression.…”

Complementary and Alternative Medicine for Vitiligo

“…Clinically, environmental factors are important in the development of vitiligo. Trauma, eczema, chemical agents, and fragility of keratinocytes play a role in development of vitiligo, so treatment decisions should be made taking these factors into account Lee et al, 2005). Historically, vitiligo was deemed to respond relatively poorly to treatment with a high recurrence rate, therefore, there is at times a reluctance to advise treatment.…”

Radiotherapy-induced depigmentation in a patient with breast cancer

“…[10] Keratinocyte apoptosis can cause lower expression of keratinocyte-derived factors, including stem cell factors and basic fibroblast growth factor. [11] These factors might be responsible for passive melanocyte death, leading to their detachment and transepidermal elimination, and may explain the KP in the vitiligo patients. Recently, however, inhibition of thioredoxin reductase by the high extracellular calcium levels observed in the keratinocytes of vitiligo patients has been also proposed.…”