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Nuclear factor E2-related factor 2 (Nrf2) is one of the most important redox-sensitive transcription factors regulating expression of antioxidative genes and cytoprotective enzymes, which constitute the cellular response to oxidative stress and xenobiotic damage. In this study, we investigated the functional role of Nrf2 during normal epidermal keratinocyte (NHEK) differentiation. Immunohistochemical staining showed that Nrf2 is expressed from basal to granular layer of epidermis. When cultured NHEKs were treated with 1.2 mM calcium, Nrf2 expression was increased gradually in protein levels and Nrf2 translocated into the nucleus in a differentiation-dependent manner. When Nrf2 was overexpressed in NHEK by adenoviral transduction, the expression of the NHEK differentiation marker loricrin and keratin 10 was increased and overexpression of Nrf2 also increased the luciferase activity of loricrin in the absence of calcium. These results suggest that Nrf2 helps to promote the differentiation of epidermal keratinocytes. [ABSTRACT FROM AUTHOR]

S100A8 and S100A9 are members of the S100 protein family and exist in neutrophils, monocytes, and macrophages. Recent studies have shown that S100A8 and S100A9 are associated with various neoplastic disorders; however, their roles in cutaneous squamous cell carcinoma (SCC) are not well defined. To investigate the expression and function of S100A8 and S100A9 in skin tumors, we examined the expression levels of S100A8 and S100A9 between premalignant and malignant skin tumors and investigated the functional roles of S100A8 and S100A9 in vitro and in vivo using recombinant adenovirus expressing S100A8 or S100A9. The immunopositive staining rates and intensities of S100A8 and S100A9 were higher in SCC than in premalignant skin tumors. When S100A8 and/or S100A9 were overexpressed in SCC12 cells using a recombinant adenovirus, cell growth and motility were increased. Similarly, when mouse skin was intradermally injected with SCC12 cells overexpressing S100A8 and/or S100A9, there were remarkable increases in tumor growth and volume. Both S100A8 and S100A9 are highly expressed in cutaneous SCC and play important roles in tumorigenesis. We suggest that S100A8 and S100A9 may be potential therapeutic targets for the prevention or treatment of SCC in skin. [ABSTRACT FROM AUTHOR]

Light-emitting diodes (LED) have been used to treat acne vulgaris. However, the efficacy of LED on sebaceous lipid production in vitro has not been examined. This study investigated the efficacy of 415 nm blue light and 630 nm red light on lipid production in human sebocytes. When applied to human primary sebocytes, 415 nm blue light suppressed cell proliferation. Based on a lipogenesis study using Oil Red O, Nile red staining, and thin-layered chromatography, 630 nm red light strongly downregulated lipid production in sebocytes. These results suggest that 415 nm blue light and 630 nm red light influence lipid production in human sebocytes and have beneficial effects on acne by suppressing sebum production.

Melanosomes are synthesized in melanocytes and transferred to neighboring keratinocytes. However, the associations of melanosome uptake with the proliferation and differentiation of keratinocytes are not fully understood. We examined the associations of melanosome uptake with keratinocyte differentiation and proliferation. SV40T-transformed human epidermal keratinocytes (SV-HEKs) were treated with isolated melanosomes. The effects of melanosome uptake on the proliferation and differentiation of the keratinocytes were analyzed by Western blotting and flow cytometry. The relationship between melanosome uptake and keratinocyte differentiation status was verified by determining the melanin content in the cells. Melanosomes reduced the proliferation of SV-HEKs in a dose-dependent manner, but did not induce differentiation. Melanosome uptake was higher in differentiating keratinocytes compared to non-differentiating keratinocytes, and inhibited significantly by PAR-2 inhibitor. Melanosomes inhibit keratinocyte proliferation. Moreover, melanosome uptake is influenced by keratinocyte differentiation status, being highest in mid-stage differentiating keratinocytes in a PAR-2 dependent manner.