Greatens Amanda, Hakozaki Tomohiro, Koshoffer Amy, Epstein Howard, Schwemberger Sandy, Babcock George, Bissett Donald, Takiwaki Hirotsugu, Arase Seiji, Wickett R Randall, Boissy Raymond E
Department of Dermatology, University of Cincinnati, Cincinnati, OH, USA.
Exp Dermatol. 2005 Jul;14(7):498-508. doi: 10.1111/j.0906-6705.2005.00309.x.
Skin pigmentation results in part from the transfer of melanized melanosomes synthesized by melanocytes to neighboring keratinocytes. Plasma membrane lectins and their glycoconjugates expressed by these epidermal cells are critical molecules involved in this transfer process. In addition, the derivative of vitamin B(3), niacinamide, can inhibit melanosome transfer and induce skin lightening. We investigated the effects of these molecules on the viability of melanocytes and keratinocytes and on the reversibility of melanosome-transfer inhibition induced by these agents using an in vitro melanocyte-keratinocyte coculture model system. While lectins and neoglycoproteins could induce apoptosis in a dose-dependent manner to melanocytes or keratinocytes in monoculture, similar dosages of the lectins, as opposed to neoglycoproteins, did not induce apoptosis to either cell type when treated in coculture. The dosages of lectins and niacinamide not affecting cell viability produced an inhibitory effect on melanosome transfer, when used either alone or together in cocultures of melanocytes-keratinocytes. Cocultures treated with lectins or niacinamide resumed normal melanosome transfer in 3 days after removal of the inhibitor, while cocultures treated with a combination of lectins and niacinamide demonstrated a lag in this recovery. Subsequently, we assessed the effect of niacinamide on facial hyperpigmented spots using a vehicle-controlled, split-faced design human clinical trial. Topical application of niacinamide resulted in a dose-dependent and reversible reduction in hyperpigmented lesions. These results suggest that lectins and niacinamide at concentrations that do not affect cell viability are reversible inhibitors of melanosome transfer.
皮肤色素沉着部分源于黑素细胞合成的黑素化黑素小体向邻近角质形成细胞的转移。这些表皮细胞表达的质膜凝集素及其糖缀合物是参与该转移过程的关键分子。此外，维生素B(3)的衍生物烟酰胺可抑制黑素小体转移并导致皮肤美白。我们使用体外黑素细胞-角质形成细胞共培养模型系统，研究了这些分子对黑素细胞和角质形成细胞活力以及这些试剂诱导的黑素小体转移抑制的可逆性的影响。虽然凝集素和新糖蛋白可在单培养中以剂量依赖性方式诱导黑素细胞或角质形成细胞凋亡，但与新糖蛋白不同，在共培养中处理时，相似剂量的凝集素不会诱导任何一种细胞类型凋亡。在黑素细胞-角质形成细胞共培养中单独或一起使用时，不影响细胞活力的凝集素和烟酰胺剂量对黑素小体转移产生抑制作用。用凝集素或烟酰胺处理的共培养物在去除抑制剂后3天恢复正常黑素小体转移，而用凝集素和烟酰胺组合处理的共培养物在这种恢复方面表现出延迟。随后，我们使用载体对照、分脸设计的人体临床试验评估了烟酰胺对面部色素沉着斑的影响。局部应用烟酰胺导致色素沉着病变呈剂量依赖性和可逆性减少。这些结果表明，不影响细胞活力浓度的凝集素和烟酰胺是黑素小体转移的可逆抑制剂。
