aging (14). It was important to distinguish previously described increase in EOTAXIN in the advanced CTCL patients (17) from normal aging. We found EOTAXIN and MIP-1B to be significantly higher across all age groups in patients with MF/SzS, suggestive of their relevance to the disease pathogenesis (Fig. S1).In conclusion, we demonstrate for the first time that the immune profiles of MF/SzS cluster closer to HIV and then to normal controls and demonstrate unique, cancer-specific and age-related immunological changes. It underscores an immunological dysbalance and immune-compromised state of patients with MF/SzS.
AcknowledgementsWe thank Sue McCann, MRN for technical support with blood collection. This work was supported by SPORE NIH 5P50CA121973-03, Project 5 (to LJG) and UL1 RR024153 from the National Center for Research Resources (NCRR).
Author contributionsLG and OA designed the study, analysed the data and wrote the paper. AL performed the Luminex assay. YL performed the statistical analysis. AL participated in the design of the work and the critical review of the paper.
Conflict of interestThe authors state no conflict of interest.
Supporting InformationAdditional Supporting Information may be found in the online version of this article: Figure S1. Age dependent biomarker expression in patient with MF/SzS and age matched controls. Table S1. Comparative analysis of soluble proteins. Medicine, Korea, Abstract: Recently, we demonstrated that leucine-rich glioma inactivated 3 (LGI3) is expressed in human skin. However, the effects of LGI3 on melanocytes remain unknown. The present study demonstrated that LGI3 can serve to stimulate melanogenesis without affecting cell viability. To determine the effects of LGI3 on melanin synthesis, normal human melanocytes and Mel-Ab cells were treated with recombinant LGI3 and melanin content was measured. Our results showed that LGI3 promoted melanin synthesis in both cell types. Moreover, upregulation of microphthalmia-associated transcription factor (MITF) and tyrosinase was observed at both the mRNA and protein levels via RT-PCR and Western blotting, respectively. Furthermore, immunohistochemical staining showed that the expression of LGI3 increased in the basal layer of melasma skin samples, whereas it decreased slightly in vitiligo samples. These results suggest that LGI3 may play a role as a melanogenic cytokine in human skin.
The purpose of this study is to characterize the effects of KHG26792 (3-(naphthalen-2-yl(propoxy) methyl)azetidine hydrochloride), a potential skin whitening agent, on melanin synthesis and identify the underlying mechanism of action. Our data showed that KHG26792 significantly reduced melanin synthesis in a dose-dependent manner. Additionally, KHG26792 downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase, the rate-limiting enzyme in melanogenesis, although tyrosinase was not inhibited directly. KHG26792 activated extracellular signal-regulated kinase (ERK), whereas an ERK pathway inhibitor, PD98059, rescued KHG26792-induced hypopigmentation. These results suggest that KHG26792 decreases melanin production via ERK activation. Moreover, the hypopigmentary effects of KHG26792 were confirmed in a pigmented skin equivalent model using Cervi cornus Colla (deer antler glue), in which the color of the pigmented artificial skin became lighter after treatment with KHG26792. In summary, our findings suggest that KHG26792 is a novel skin whitening agent.
A few types of ceramide are reported to decrease melanin synthesis. In the present study, we examined the effects of an artificial ceramide analog, PC102, on melanogenesis using a spontaneously immortalized melanocyte cell line (Mel-Ab). PC102 is currently used as a moisturizing additive in a variety of cosmetics. Our data showed that PC102 inhibited melanin production and tyrosinase activity in a dose-dependent manner, but did not directly affect tyrosinase activity. Microphthalmia-associated transcription factor (MITF), tyrosinase, and β-catenin protein levels decreased after 48 h of PC102 treatment. In contrast, PC102 did not decrease MITF, tyrosinase, and β-catenin mRNA levels. Therefore, we investigated whether the decrease in MITF and tyrosinase by PC102 is due to proteasomal degradation. MG132, a proteasomal inhibitor, completely abolished tyrosinase downregulation due to PC102 and partially reduced the downregulation of MITF and β-catenin due to PC102. Moreover, MG132 abrogated the inhibition of melanin synthesis by PC102. Taken together, our data suggest that PC102 may inhibit melanin synthesis through MITF and tyrosinase degradation.
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