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.
Dr. Genji Imokawa (Ph.D.-medicine) now is Professor of Utsunomiya University, Center for Bioscience Research and Education as well as Visiting Professor of Chubu University, Research Institute of Biological Functions and of Ohio University, Edison Biotechnology Institute. Board of Directors in Japanese Society for Ceramide Research and Japanese Medical Society for Skin Aging and Council member for Japanese Medical Society for Anti-Aging. Research Activities: More than 175 original English papers including EMBO Journal, J Clinical Invest, J Cell Sci, Cancer Res, Am J Pathol, FASEB J, J Biol Chem, J Pathol and J Lipid Res; Research Field: Photo-aging/ Fibroblasts, Atopic Dermatitis/Sphingolipid Metabolism, Melanogenesis/Melanocyte Biology, Keratinization/Keratinocyte Biology.