Melanocyte Activation Mechanisms and Rational Therapeutic Treatments of Solar Lentigos

Genji Imokawa

doi:10.3390/ijms20153666

Abstract

To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1/endothelin B receptors (EDNBRs), stem cell factor (SCF)/c-KIT, and tumor necrosis factor (TNF)α in the lesional epidermis, which contrasted with the downregulated expression of interleukin (IL) 1α. These findings strongly support the hypothesis that previous repeated UVB exposure triggers keratinocytes to continuously produce TNFα. TNFα then stimulates the secretion of EDNs and the production of SCF in an autocrine fashion, leading to the continuous melanogenic activation of neighboring melanocytes, which causes SLs. A clinical study of 36 patients with SLs for six months treated with an M. Chamomilla extract with a potent ability to abrogate the EDN1-induced increase in DNA synthesis and melanization of human melanocytes in culture revealed a significant improvement in pigment scores and color differences expressed as L values. Another clinical study using a tyrosinase inhibitor L-ascorbate-2-phosphate 3 Na (ASP) demonstrated that L values of test lotion (6% APS)-treated skin significantly increased in SLs and in non-lesional skin with a significantly higher ΔL value in SLs when compared with non-lesional skin. The sum of these findings strongly suggests that combined topical treatment with EDN signaling blockers and tyrosinase inhibitors is a desirable therapeutic choice for SLs.

Highlights

The most frequently appearing epidermal hyperpigmentary disorder in Asian skin is solar lentigos (SLs), which generally occur on the face and on the dorsum of the hands
In contrast to UVB-induced hyperpigmentation (UVB melanosis), which, depending on the age of the subject, disappears within two weeks to a few months after discontinuation of the UVB exposure, SLs develop on sun-exposed skin, especially the face, and never disappear due to possible DNA damage in the keratinocytes elicited by repeated UVB irradiation of the lesional epidermis
As for the mechanism underlying the increased expression of stem cell factor (SCF) in SLs, we examined the effects of TNFα on SCF expression in cultured human keratinocytes

Summary

Introduction

The most frequently appearing epidermal hyperpigmentary disorder in Asian skin is solar lentigos (SLs), which generally occur on the face and on the dorsum of the hands.

Results

Conclusion