Downregulation of nuclear factor‐kappaB activation in human keratinocytes by melanogenesis inhibitors

Abstract

Liberated nuclear factor‐kappaB (NF‐κB) is translocated into the nucleus where it can change or alter the expression of target genes, resulting in the secretion of extracellular signaling molecules including melanotrophic factors affecting the melanocyte. In order to demonstrate the possible role of NF‐κB activation on the synthesis of melanotrophic factors from the keratinocytes, the activities of NF‐κB induced by melanogenesis inhibitors were determined in human HaCaT keratinocytes transfected with pNF‐κB‐SEAP‐NPT plasmid. Transfectant cells released the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the NF‐kB activity. Melanogenesis inhibitors such as niacinamide, kojic acid, hydroquinone, resorcinol, arbutin and glycolic acid were pre‐incubated with transfectant HaCaT cells for 3 h and then irradiated with ultraviolet B (UVB). Of the melanogenesis inhibitors tested, kojic acid (IC50 = 60 μM) was found to be the most potent inhibitor of UVB‐upregulating NF‐κB activation in transfectant HaCaT cells, which is followed by niacinamide (IC50 = 540 μM). Especially kojic acid and niacinamide effectively lowered NF‐κB binding as measured by the electrophoretic mobility shift assay. Furthermore, these two inhibitors remarkably reduced the secretion level of IL (interleukin)‐6, one of the melanotrophic factors, triggered by UV radiation of the HaCaT cells. These observations suggest that melanogenesis inhibitors working at the in vivo level might act partially through the modulation of the synthesis of melanotrophic factors in keratinocytes.