Our observations indicate that skin sensitivity differs considerably between women from different parts of China and South Korea. We recommend that these differences be considered during the development of cosmetic products in these countries.

Granulomatous rosacea (GR) is a variant of rosacea. Ultraviolet radiation (UVR) is considered to be etiologically related to GR, but its pathogenesis still remains unclear. Although, recent studies suggested that transient receptor potential vanilloid (TRPV) and mast cells are involved in the pathogenesis of rosacea, their role in each variants of rosacea such as GR has not been reported. In this respect, this study was conducted to investigate immunohistochemical expression of MMP-1, -9, TRPV, and CD117 in the GR compared with the non-granulomatous rosacea (NGR) and to test the hypothesis that immunohistochemical expressions of GR would relate with UVR. Biopsy samples were obtained from 11 patients of GR and 11 patients of NGR. For the analysis, subjects in two groups were age-matched. The sections were stained using hematoxylin and eosin, and antibodies MMP-1, -9, TRPV, and CD117. And expression of antibodies was evaluated with a semi-quantitative scale. The expression of MMP-1, -9, and TRPV was significantly increased in GR lesions compared with NGR lesions (p < 0.05), especially at the center of granulomas. CD117 expression was increased in GR lesions, although difference between the two groups was not statistically significant. We suggest that, in GR lesions, TRPV is associated significantly with granuloma formation as well as MMP-1, -9 in relation to UVR exposure, and mast cells may play an important role in this process. 724Protection against photo-aging by targeting the transient receptor potential channel, TRPV1 2 The Estee Lauder Companies, Melville, NY and 3 The Estee Lauder Companies and Clinique Laboratories, Melville, NY Photo-aging, due to repetitive exposure to solar radiation, is linked to the premature development of wrinkles and skin sagging. Solar radiation is composed of a spectrum of electromagnetic radiation that is divided into three categories based on wavelength: ultraviolet (UV), visible, and infrared (IR). It is established that prolonged exposure to UV radiation has deleterious effects on skin; however, recent evidence suggests that precipitous aging of the skin is also influenced by IR radiation that comprises w54% of solar radiation. It has been demonstrated, in vivo that IR-induced heating and UV radiation up-regulate and activate TRPV1 channels, which has been shown to induce collagen degradation via the up-regulation of the matrix metalloprotease, MMP-1, contributing to photo-aging. We sought to investigate if an antagonist of TRPV1, 4-t-butylcyclohexanol, would protect against IR and UV radiation. To address this, reconstructed human skins were irradiated with IR or UV light once a day for 2 days in the presence or absence of the TRPV1 antagonist. Transepithelial Electrical Resistance (TEER) measurements, immunochemical assays, and histological analysis were used to determine modifications in skin barrier, cytokine release, and protein expression, respectively. TEER data revealed that modulating TRPV1 activation markedly improved barrier integrity. The pro-inflammatory cytokines...

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Seoul-t'ukpyolsi, Republic of Korea Acral melanoma is of particular interest to understand melanoma pathogenesis, because it is invasive and treatment-resistant, but not associated with sun exposure. We studied gene expression profiles of human acral melanoma (n¼10) compared to non-acral melanoma (n¼21 for array, n¼5 for PCR), paired non-melanoma tissues of the melanoma patients (n¼11), and acral (n¼7) or non-acral (n¼12) healthy skin from volunteers by utilizing IHC, RT-PCR, and gene arrays. Hallmark melanoma genes (MLANA, MITF, PRAME, and MAGEA12) were equivalently enriched in both acral and non-acral melanoma compared to paired non-melanoma or normal skin. Keratinocyte proliferation marker (KRT16) was higher in acral melanoma compared to non-acral melanoma or normal skin. T cell and dendritic cell activation was high both in acral and non-acral melanoma based on expression of CD2, CD3, CD8, CD86, DC-LAMP, ITK, and JAK3 mRNAs; high interferon pathway activation was also detected. Importantly, a key molecular distinction was lower expression of negative immune regulatory genes (FoxP3, FAS, CTLA4, PD-1, PD-1 L1, PD-1 L2, IL-10, P53, CD69) in acral melanoma compared to non-acral melanoma. Gene set variation analysis also revealed lower regulatory T cell vs. conventional T cell signature in acral melanoma compared to non-acral melanoma. We thus hypothesize that negative immune regulators are less activated in the tumor microenvironment of acral melanoma, suggesting treatment-resistant mechanism of acral melanoma to immunotherapies targeting negative regulators of T cells.

The breakdown and molecular size of Hyaluronan (HA) has been hypothesized to influence wound healing, but direct evidence of this has not been obtained. To test if the breakdown of HA acts as an endogenous signal of injury we generated transgenic mice that conditionally overexpressed Hyaluronidase 1 (HYAL1). When HYAL1 was constitutively expressed in early embryogenesis (EIIa/HYAL1), these mice showed extensive degradation of HA in the dermis yet were morphologically normal. When these mice were wounded by full-thickness 6 mm punch biopsy, wound closure was delayed by approximately 2 days in EIIa/HYAL1 compared to control mice (p<0.001). To examine the dynamic nature of epidermal response to expression of HYAL1, we next evaluated the wound healing in the tamoxifen-inducible K14-dependent Cre system and wound closure was delayed in K14CreERT/HYAL1 (p<0.001). Re-epithelialization is a key event in wound healing. To determine if delayed wound healing was due to the regulation of keratinocyte migration, we harvested the keratinocytes from the transgenic mice and performed the wound scratch assays. The keratinocytes from EIIa/HYAL1 mice showed significantly impared migration (p<0.001). Furthermore, delayed repair may result from abnormal macrophage polarization in wound tissues 48 hours after wounding as we found a significantly higher M1/M2 macrophage ratio in EIIa/HYAL1 mice (p<0.05). Histological and flow cytometirc evaluation of the skin wounds at 96 hours showed significantly more inflammatory cell infiltration in EIIa/HYAL1 mice (p<0.05). To exclude the effects that are unrelated to HA degradation, we injected the tetrasaccharide HA right after wounding and found that the injection delayed wound healing significantly. These data show that abnormal degradation of hyaluronan modulates wound healing and suggests targeting this pathway may be therapeutically useful in treatment of abnormal wound repair.