These results suggest that the low hydration state of dry skin may be due to the reduction in (pro)filaggrin degradation caused by decreased bleomycin hydrolase expression.

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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Frontal fibrosing alopecia (FFA) is a devastating, progressive scarring alopecia with increasing worldwide prevalence. Its pathogenesis is unknown, leading to lack of targeted therapeutics. We sought to elucidate the molecular profile of lesional and non-lesional scalp from patients with FFA (n¼12) as compared with alopecia areata (AA) (n¼10) and healthy control scalp (n¼3). Overall, FFA tissues showed higher induction of key T H 1 (IFN-g, CXCL9, CXCL10; p<0.05), and JAK-STAT signaling and T-cell activation mediators (JAK3, STAT1, IL-2RA; p<0.05), in FFA lesional, but also in non-lesional scalp, compared with controls and AA tissues. Several T H 2/T H 9 markers, such as IL-10 (p<0.01), CCL13 (p<0.01), IL-13, and IL-9 were also upregulated in FFA lesions. The T H 17/T H 22-regulated marker S100A7 was upregulated in FFA lesions (p<0.01), and its expression also significantly correlated with clinical severity (as measured by FFA Severity Index [FFASI]) in patients with more severe disease (p<0.05). Hair keratins did not show decreased expression in FFA, unlike in AA in which these genes (KRTAP1, KRT40, KRT75, KRT83, KRT84, KRT86) showed characteristically significant suppressions versus control scalp (p<0.05). This is the first study to characterize the molecular fingerprinting of FFA tissues. Our data suggests that FFA is a highly inflammatory disease already at the non-lesional state, with predominant T H 1 and JAK-STAT pathway involvement without inhibition of hair keratins, the hallmark of AA. These findings identify JAK-STAT signaling as a potential therapeutic target for this debilitating disease.

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