Transcriptomic Analysis of Human Keratinocytes Treated with Galactomyces Ferment Filtrate, a Beneficial Cosmetic Ingredient.

Galactomyces ferment filtrate (GFF, Pitera™) is a cosmetic ingredient known to have multiple skin care benefits, such as reducing redness and pore size via the topical application of its moisturizer form. Although GFF is known to act partly as an antioxidative agonist for the aryl hydrocarbon receptor (AHR), its significance in keratinocyte biology is not fully understood. In this study, we conducted a transcriptomic analysis of GFF-treated human keratinocytes. Three different lots of GFF consistently modulated 99 (22 upregulated and 77 downregulated) genes, including upregulating cytochrome P450 1A1 (CYP1A1), a specific downstream gene for AHR activation. GFF also enhanced the expression of epidermal differentiation/barrier-related genes, such as small proline-rich proteins 1A and 1B (SPRR1A and SPRR1B), as well as wound healing-related genes such as serpin B2 (SERPINB2). Genes encoding components of tight junctions claudin-1 (CLDN1) and claudin-4 (CLDN4) were also target genes upregulated in the GFF-treated keratinocytes. In contrast, the three lots of GFF consistently downregulated the expression of inflammation-related genes such as chemokine (C-X-C motif) ligand 14 (CXCL14) and interleukin-6 receptor (IL6R). These results highlight the beneficial properties of GFF in maintaining keratinocyte homeostasis.

A Potential Role of Keratinocyte-Derived Bilirubin in Human Skin Yellowness and Its Amelioration by Sucrose Laurate/Dilaurate.

Sallow and/or dull skin appearance is greatly attributable to the yellow components of skin tone. Bilirubin is a yellow chromophore known to be made in the liver and/or spleen and is transported throughout the body via the blood stream. Recent publications suggest bilirubin may be synthesized in other cells/organs, including the skin. We found human keratinocytes express the transcripts involved in bilirubin biosynthesis. In parallel, we also found human keratinocytes could indeed synthesize bilirubin in monolayer keratinocytes and in a 3D human skin-equivalent model. The synthesized amount was substantial enough to contribute to skin yellowness. In addition, oxidative stress enhanced bilirubin production. Using UnaG, a protein that forms a fluorescent species upon binding to bilirubin, we also visualized the intracellular expression of bilirubin in keratinocytes. Finally, we screened a compound library and discovered that the sucrose laurate/dilaurate (SDL) combination significantly reduced bilirubin levels, as well as bilirubin-mediated yellowness. In conclusion, bilirubin is indeed synthesized in epidermal keratinocytes and can be upregulated by oxidative stress, which could contribute to chronic or transient yellow skin tone appearance. Application of SDL diminishes bilirubin generation and may be a potential solution to mitigate yellowish and/or dull skin appearance.

A framework to mitigate the risk of chemical leukoderma: Consumer products.

Chemical leukoderma is an acquired depigmentation of the skin caused by repeated exposure to specific agents damaging to epidermal melanocytes. Case reports of chemical leukoderma have been associated with some consumer products. To date, there are no well-accepted approaches for evaluating and minimizing this risk. To this end, a framework is presented that evaluates the physical and chemical characteristics of compounds associated with chemical leukoderma and employs structure-activity relationship (SAR) read-across and predictive metabolism tools to determine whether a compound is at increased risk of evoking chemical leukoderma. In addition to in silico approaches, the testing strategy includes in chemico quinone formation and in vitro melanocyte cytotoxicity assays to dimension the risk as part of an overall weight of evidence approach to risk assessment. Cosmetic ingredients raspberry ketone, undecylenoyl phenylalanine, tocopheryl succinate, p-coumaric acid, resveratrol, resveratrol dimethyl ether, sucrose dilaurate, tranexamic acid, niacinamide and caffeic acid are evaluated in this framework and compared to positive controls rhododendrol and hydroquinone. Overall, this framework is considered an important step toward mitigating the risk of chemical leukoderma for compounds used in consumer products.

Niacinamide mitigates SASP-related inflammation induced by environmental stressors in human epidermal keratinocytes and skin.

OBJECTIVE: To evaluate whether niacinamide (Nam) can mitigate production of inflammatory and senescence-related biomarkers induced by environmental stressors. METHODS: Human epidermal keratinocytes were exposed to UVB, urban dust, diesel exhaust and cigarette smoke extract and treated with Nam or vehicle control. Full thickness 3-D skin organotypic models were exposed to a combination of UVB and PM2.5 and treated with Nam or vehicle control. Quantitation of the SASP-related inflammatory mediators PGE2 , IL-6 and IL-8 was performed on cultured media. UVB-exposed keratinocytes treated with and without Nam were immunostained for the senescence biomarker Lamin B1 (LmnB1). Transcriptomics profiling of cigarette smoke extract effects on keratinocytes was performed. A double-blind, placebo-controlled clinical was conducted on 40 female panellists that were pretreated on back sites for two weeks with 5% Nam or vehicle and then exposed to 1.5 minimal erythemal dose (MED) solar-simulated radiation (SSR). Treated sites were compared with non-treated exposed sites for erythema and the skin surface IL-1αRA/IL-1α inflammatory biomarkers. RESULTS: Ultraviolet B induced synthesis of PGE2 , IL-8 and IL-6 and reduced LmnB1 levels in keratinocytes. Urban dust and diesel exhaust only stimulated synthesis of IL-8 whereas cigarette smoke extract only stimulated levels of PGE2 . In all exposures, treatment with Nam significantly mitigated synthesis of the inflammatory mediators and restored levels of UVB-reduced LmnB1. In the 3D skin equivalent model, Nam reduced IL-8 levels stimulated by a combination of topical PM2.5 and UV exposure. In a UV challenge clinical, pretreatment with 5% Nam reduced erythema and skin surface IL-1αRA/IL-1α inflammatory biomarkers that were induced by SSR. CONCLUSION: Since it is known that Nam has anti-inflammatory properties, we tested whether Nam can inhibit environmental stress-induced inflammation and senescence-associated secretory phenotype (SASP) biomarkers. We show Nam can reduce PGE2 , IL-6 and IL-8 levels induced by environmental stressors. Additionally, in vivo pretreatment with Nam can reduce UV-induced erythema and skin surface inflammatory biomarkers. These findings add to the body of evidence that Nam can mitigate the skin's inflammatory response elicited by environmental stressors. This supports Nam can potentially inhibit senescence and premature ageing and thereby maintain skin's functionality and appearance.

OBJECTIF: Évaluer si le niacinamide (Nam) peut atténuer la production de biomarqueurs inflammatoireset liés à la sénescence induits par les facteurs de stress environnementaux. MÉTHODES: Leskératinocytes épidermiques H uman ont été exposés aux UVB, à la poussière urbaine, aux gaz d'échappement diesel et à l'extrait de fumée de cigarette et traités avec nam ou contrôle de véhicule. Les modèles organotypic de peau 3D de pleine épaisseur ont été exposés à une combinaison d'UVB et de PM2.5 et traités avec nam ou commande de véhicule. La quantitation des médiateurs inflammatoires liés à la SASP PGE2 ,IL-6 et IL-8 a été réalisée sur des médias cultivés. Les kératinocytes exposés aux UVB traités avec et sans Nam étaient immunotachés pour le biomarqueur de sénescence Lamin B1 (LmnB1). Le profilage de transcriptomique des effets d'extrait de fumée de cigarette sur les kératinocytes a été exécuté. Un placebo contrôlé clinique à double insu a été menée sur 40 panélistes féminins qui ont été prétraités sur les sites arrière pendant deux semaines avec 5% Nam ou véhicule, puis exposés à 1,5 dose erythémique minimale (MED) rayonnement solaire simulé (SSR). Les sites traités ont été comparés à des sites exposés non traités pour l'érythème et la surface de la peau IL-1▫RA/IL-1▫ biomarqueurs inflammatoiress. RÉSULTATS: Synthèse induite par UVB des niveaux de PGE2, IL-8 et IL-6 et réduit de LmnB1 dans les kératinocytes. La poussière urbaine et les gaz d'échappement diesel n'ont stimulé que la synthèse de l'IL-8 alors que l'extrait de fumée de cigarette ne stimulait que les niveaux de PGE2 . Dans toutes les expositions, le traitement avec Nam a significativement atténué la synthèse des médiateurs inflammatoires et les niveaux restaurés de LmnB1 UVB-réduit. Dans le modèle équivalent de la peau 3D, Nam a réduit les niveaux d'IL-8 stimulés par une combinaison de PM combination of topical PM 2.5 topique et d'exposition aux UV. Dans un uv-défi clinique, prétraitement avec 5% Nam réduit érythème et la surface de la peau IL-1▫RA/IL-1▫ biomarqueurs inflammatoires qui ont été induits par SSR. CONCLUSION: Puisqu'il est connu que Nam a des propriétés anti-inflammatoires, nous avons testé si Nam peut inhiber l'inflammation induite par le stressenvironnementaltion et les biomarqueurs sécrétoires sécrétoires sécrétoires (SASP) associés à la sénescence. We montrent Nam peut réduire PGE2 ,IL-6, et IL-8 niveaux induits par les facteurs de stress environnementaux. En outre, le prétraitement in vivo avec Nam peut réduire l'érythème induit par les UV et les biomarqueurs inflammatoires de surface de la peau. Ces résultats ajoutent à l'oody bde la preuve que Nam peut atténuer la réponse inflammatoire de la peau provoquée par lesfacteurs de stress environnementaux. Cela soutient Nam peut potentiellement inhiber la sénescence et le vieillissement prématuré et ainsi maintenir la fonctionnalité de la peau et l'apparence.