Summary Background Melanism is more frequent in animals living in polluted areas on urban–industrial sites. Given that an increasing number of people are exposed to elevated air pollution levels, it is possible that environmental pollutants affect melanogenesis in human skin. Epidemiological studies have shown that exposure to traffic‐related air pollutants such as diesel exhaust particles (DEP) is associated with more clinical signs of hyperpigmentation. However, mechanistic evidence linking DEP exposure to pigmentation has been elusive. Objectives To develop an ex␣vivo skin model to allow for repetitive topical application of relevant ambient DEP, and to provide proof of concept in humans. Methods We measured skin pigmentation, melanin and pigmentation‐associated gene expression, and evaluated oxidative stress. Results Repetitive exposure of ex␣vivo skin to DEP at nontoxic concentrations increased skin pigmentation. This increase was visible to the naked eye, time dependent, and associated with an increase in melanin content and the transcription of genes involved in de novo melanin synthesis. Similarly, in healthy participants (n = 76), repetitive topical application of DEP at nontoxic concentrations increased skin pigmentation. DEP‐induced pigmentation was mediated by an oxidative stress response. After the application of DEP, epidermal antioxidants were depleted, lipid peroxidation and oxidative DNA damage were enhanced, and in a vehicle‐controlled, double‐blind clinical study DEP‐induced pigmentation was prevented by the topical application of an antioxidant mixture. Conclusions Similar to solar radiation, air pollutants cause skin tanning. As eumelanin is an antioxidant, it is proposed that this response serves to protect human skin against air pollution‐induced oxidative stress.
Cockayne syndrome (CS), a hereditary form of premature aging predominantly caused by mutations in the gene, affects multiple organs including skin where it manifests with hypersensitivity toward ultraviolet (UV) radiation and loss of subcutaneous fat. There is no curative treatment for CS, and its pathogenesis is only partially understood. Originally considered for its role in DNA repair, Cockayne syndrome group B (CSB) protein most likely serves additional functions. Using CSB-deficient human fibroblasts,, and mice, we show that CSB promotes acetylation of α-tubulin and thereby regulates autophagy. At the organ level, chronic exposure of mice to UVA radiation caused a severe skin phenotype with loss of subcutaneous fat, inflammation, and fibrosis. These changes in skin tissue were associated with an accumulation of autophagic/lysosomal proteins and reduced amounts of acetylated α-tubulin. At the cellular level, we found that CSB directly interacts with the histone deacetylase 6 (HDAC6) and the α-tubulin acetyltransferase MEC-17. Upon UVA irradiation, CSB is recruited to the centrosome where it colocalizes with dynein and HDAC6. Administration of the pan-HDAC inhibitor SAHA (suberoylanilide hydroxamic acid) enhanced α-tubulin acetylation, improved autophagic function in CSB-deficient models from all three species, and rescued the skin phenotype in mice. HDAC inhibition may thus represent a therapeutic option for CS.
Vitiligo is a chronic autoimmune depigmentation disorder affecting up to 152 million people worldwide, with increased prevalence among skin of color individuals in whom the disease is more noticeable. It has a profound negative impact on patient quality of life and lacks effective therapeutic options. While the current pathogenic paradigm highlights T H 1/IFNgupregulation, limited blood data also suggests possible involvement of other cytokine axes. We sought to investigate the genomic profile in lesional and non-lesional tissues of patients with vitiligo (n¼16) as compared with control skin (n¼8). We found significant upregulation of multiple immune pathways in both lesional and non-lesional vitiligo skin versus controls. These included significant increases in T H 1 markers (i.e. IFNg, CXCL9, CXCL10, and CCL5; p<0.01), but also in key T H 2 cytokines and chemokines (i.e. IL-5, IL-13; p<0.05, CCL13, and CCL18; p<0.01). Less consistent and significant increases were detected in some T H 17/T H 22 markers (i.e. IL-17A, IL-22, and S100A9; p<0.05), mostly in lesional skin only. Key mediators of JAK/STAT signaling (JAK3, STAT1) were significantly upregulated in both lesional and nonlesional tissues, as was the general inflammation marker MMP12 (p<0.05 for all). Overall, our data expands the current understanding of cytokine pathways in vitiligo skin beyond T H 1 skewing, providing a basis for possible future therapeutic targeting for patients with vitiligo.
the Republic of) and 2 Hisol, Namwon, Korea (the Republic of) Development of new efficient cosmeceuticals is one of hot competitive fields in skin research due to its potential as new therapeutic modalities besides their original concept of supportive care. As candidate materials for new cosmeceuticals, herb extracts are regarded to be ideal candidates due to their known safety in human bodies. This study was performed to determine the antioxidant activity of essential oils and hydrosols, which extracted from naturallyoccurring herbs in NHEKs. To select candidate herb products with a potent antioxidant activity, cells were treated with the following products: Lavernder; Lemongrass; Rosemary; Peppermint; and Chamomile oil and hydrosol, respectively. To determine the scavenging activity of products, cells were treated with 50 mJ/cm 2 of UVB, and then immediately harvested for assaying total ROS levels by using the DCFDA-cellular reactive oxygen species detection assay kit. To determine antioxidant expression levels, NHEKs were treated with oil and hydros products for 24 hrs, and RT-PCR and Western blot analysis were performed. In DCFDA assay by FACS analysis and confocal microscopic experiments, all of tested herb products have a ROS-scavenging activities to inhibit UVB-induced ROS production. In RT-PCR and Western blot analysis, all of tested products induced the up-regulation of expression levels of Cu-zn SOD, MnSOD, GPx II, Prx I and a set of Nrf-2-dependent phase 2 enzymes, such as HO-1, NQO-1, GSTA4, GSTpi, in a dose-dependent manner. Nrf-2 transcriptional factor was up-regulated as it was translocated to the nucleus, indicating the Nrf-2-dependent modulation of phase 2 enzymes. In summary, our tested herb extracts of oil products and hydrosol are revealed to have a potent antioxidant activity by modulating ROS-scavenging enzymatic antioxidants and Nrf 2-dependent phase 2 enzymes in NHEKs. From our study, we propose a set of candidate herb extracts, which can be used for important sources for new cosmeceuticals in future.
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