Koichiro Kameyama

Inhibitory effect of magnesium l-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo

BACKGROUND An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been described. However, AsA is quickly oxidized and decomposed in aqueous solution and thus is not generally useful as a depigmenting agent. OBJECTIVE Our purpose was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of AsA. METHODS Percutaneous absorption of VC-PMG was examined in dermatomed human skin, and its effect on melanin production by mammalian tyrosinase and human melanoma cells in culture was also measured. A 10% VC-PMG cream was applied to the patients. RESULTS VC-PMG suppressed melanin formation by tyrosinase and melanoma cells. In situ experiments demonstrated that VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours after application. The lightening effect was significant in 19 of 34 patients with chloasma or senile freckles and in 3 of 25 patients with normal skin. CONCLUSION VC-PMG is effective in reducing skin hyperpigmentation in some patients.

Treatment of reticulate acropigmentation of Kitamura with azelaic acid: An immunohistochemical and electron microscopic study

No successful therapy has been reported for reticulate acropigmentation of Kitamura, which is an autosomal dominant dermatosis. We treated a patient with 20% azelaic acid ointment. Within several weeks the pigmentation was remarkably decreased and no side effects were observed. Histologic examination revealed an increased number of dopa-positive melanocytes. These cells reacted strongly to staining with antityrosinase antibody or antityrosinase-related protein antibody. Electron microscopic findings showed many melanosomes within melanocytes, keratinocytes, and melanophages. These findings suggest that the hyperpigmentation of reticulate acropigmentation of Kitamura is the result of an excess amount of melanin production caused by activation of melanocytes in the basal layer.

Recombinant gamma interferon induces HLA-DR expression on squamous cell carcinoma, trichilemmoma, adenocarcinoma cell lines, and cultured human keratinocytes

SummaryWe investigated the effects of recombinant human gamma interferon on the induction of HLA-DR expression by two human squamous cell carcinoma, three trichilemmoma, one eccrine carcinoma, two adenocarcinoma cell lines, and cultured human keratinocytes in vitro. None of eight epithelial cell lines or keratinocytes expressed HLA-DR without gamma interferon treatment. In contrast, pure gamma interferon (500 IU/ml, 72-h treatment) induced HLA-DR expression on 1/2 squamous cell carcinoma, 3/3 trichilemmoma, 2/2 adenocarcinoma cell lines, and 4/4 kerationcyte cell lines, as determined using a fluorescence-activated cell sorter. A maxillary squamous cell carcinoma line and an eccrine carcinoma cell line failed to express HLA-DR with gamma interferon treatment; however, the growth of cells was inhibited by gamma interferon treatment. By indirect immunoperoxidase techniques, tumor cells such as Bowens disease and squamous cell carcinoma were found to express HLA-DR. Since HLA-DR expression has been shown to be important for various immune responses, these findings suggest that gamma interferon plays important roles in various immune-related skin diseases.

Pigment production in murine melanoma cell is regulated by tyrosinase, tyrosinase-related protein 1 (TRP1), dopachrome tautomerase(TRP2), and a melanogenic inhibitor

Using antibodies that recognize either tyrosinase, tyrosinase-related protein-1 (TRP1), or tyrosinase-related protein-2 (TRP2, DOPAchrome tautomerase), the quantities of those melanogenic enzymes were analyzed in five melanoma cell lines that possess various degrees of melanin production. All cells except JB/MS-W increased melanin production four to 30 times after 4 d of melanocyte-stimulating hormone (MSH) treatment. Melanin production by JB/MS-W cells was always under background, with or without MSH treatment. There was a positive correlation between quantities and synthetic rates of those melanogenic enzymes and their melanin formation or DOPAchrome tautomerase activities. The activity of a heat-resistant melanogenic inhibitory factor was also analyzed. The results showed, surprisingly, that pigmented cells showed higher levels of melanogenic inhibitors activity. Tyrosinase activity was increased dramatically whereas the level of melanogenic inhibitor was remarkably decreased following MSH treatment. Interestingly, melanogenic inhibitor derived from JB/MS-W cells suppressed not only tyrosinase but also DOPAchrome tautomerase, another enzyme functional in melanin production. These results clearly suggest that melanin production is regulated by a subtle balance between the activities of these enzymes and other factors such as the melanogenic inhibitor.