scholarly journals Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model

Allergy ◽  
2012 ◽  
Vol 68 (1) ◽  
pp. 37-47 ◽  
Author(s):  
M. Gschwandtner ◽  
M. Mildner ◽  
V. Mlitz ◽  
F. Gruber ◽  
L. Eckhart ◽  
...  
Keyword(s):  
Human Skin ◽  
Barrier Function ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Skin Model ◽  
Epidermal Keratinocyte

scholarly journals EGFR inhibitors switch keratinocytes from a proliferative to a differentiative phenotype affecting epidermal development and barrier function

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nicolas Joly-Tonetti ◽  
Thomas Ondet ◽  
Mario Monshouwer ◽  
Georgios N. Stamatas
Keyword(s):  
Growth Factor ◽  
Barrier Function ◽  
Kinase Inhibitors ◽  
Treatment Protocol ◽  
Growth Factor Receptor ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Epidermal Keratinocytes ◽  
Epidermal Structure

Abstract Background Cutaneous adverse drug reactions (CADR) associated with oncology therapy involve 45–100% of patients receiving kinase inhibitors. Such adverse reactions may include skin inflammation, infection, pruritus and dryness, symptoms that can significantly affect the patient’s quality of life. To prevent severe skin damages dose adjustment or drug discontinuation is often required, interfering with the prescribed oncology treatment protocol. This is particularly the case of Epidermal Growth Factor Receptor inhibitors (EGFRi) targeting carcinomas. Since the EGFR pathway is pivotal for epidermal keratinocytes, it is reasonable to hypothesize that EGFRi also affect these cells and therefore interfere with the epidermal structure formation and skin barrier function. Methods To test this hypothesis, the effects of EGFRi and Vascular Endothelial Growth Factor Receptor inhibitors (VEGFRi) at therapeutically relevant concentrations (3, 10, 30, 100 nM) were assessed on proliferation and differentiation markers of human keratinocytes in a novel 3D micro-epidermis tissue culture model. Results EGFRi directly affect basal keratinocyte growth, leading to tissue size reduction and switching keratinocytes from a proliferative to a differentiative phenotype, as evidenced by decreased Ki67 staining and increased filaggrin, desmoglein-1 and involucrin expression compared to control. These effects lead to skin barrier impairment, which can be observed in a reconstructed human epidermis model showing a decrease in trans-epidermal water loss rates. On the other hand, pan-kinase inhibitors mainly targeting VEGFR barely affect keratinocyte differentiation and rather promote a proliferative phenotype. Conclusions This study contributes to the mechanistic understanding of the clinically observed CADR during therapy with EGFRi. These in vitro results suggest a specific mode of action of EGFRi by directly affecting keratinocyte growth and barrier function.

scholarly journals Assessment of Human Skin Gene Expression by Different Blends of Plant Extracts with Implications to Periorbital Skin Aging

2018 ◽  
Vol 19 (11) ◽  
pp. 3349 ◽  
Author(s):  
Jin Namkoong ◽  
Dale Kern ◽  
Helen Knaggs
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Human Skin ◽  
Barrier Function ◽  
Skin Barrier ◽  
Skin Aging ◽  
Skin Barrier Function ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
And Oxidative Stress

Since the skin is the major protective barrier of the body, it is affected by intrinsic and extrinsic factors. Environmental influences such as ultraviolet (UV) irradiation, pollution or dry/cold air are involved in the generation of radical oxygen species (ROS) and impact skin aging and dermal health. Assessment of human skin gene expression and other biomarkers including epigenetic factors are used to evaluate the biological/molecular activities of key compounds in cosmetic formulas. The objective of this study was to quantify human gene expression when epidermal full-thickness skin equivalents were exposed to: (a) a mixture of betaine, pentylene glycol, Saccharomyces cerevisiae and Rhodiola rosea root extract (BlendE) for antioxidant, skin barrier function and oxidative stress (with hydrogen peroxide challenge); and (b) a mixture of Narcissus tazetta bulb extract and Schisandra chinensis fruit extract (BlendIP) for various biomarkers and microRNA analysis. For BlendE, several antioxidants, protective oxidative stress biomarkers and many skin barrier function parameters were significantly increased. When BlendE was evaluated, the negative impact of the hydrogen peroxide was significantly reduced for the matrix metalloproteinases (MMP 3 and MMP 12), the skin aging and oxidative stress biomarkers, namely FBN2, ANXA1 and HGF. When BlendIP was tested for cell proliferation and dermal structural components to enhance the integrity of the skin around the eyes: 8 growth factors, 7 signaling, 7 structural/barrier function and 7 oxidative stress biomarkers were significantly increased. Finally, when BlendIP was tested via real-time RT-PCR for microRNA expression: miR-146a, miR-22, miR155, miR16 and miR21 were all significantly increased over control levels. Therefore, human skin gene expression studies are important tools to assess active ingredient compounds such as plant extract blends to advance dermal hypotheses toward validating cosmetic formulations with botanical molecules.

scholarly journals The Effect of Ultra Fine Bubbles Water on the Human skin

2021 ◽  
Author(s):  
Yuji Kato ◽  
Tomoyuki Matsumoto ◽  
Setsuko Koura
Keyword(s):  
Stratum Corneum ◽  
Human Skin ◽  
Barrier Function ◽  
Water Clusters ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Small Water ◽  
High Affinity ◽  
Normal Water ◽  
Large Clusters

A certain amount of water needs to be maintained in the stratum corneum of the skin in order to maintain the skin barrier function. Therefore, it is important to supply water to the stratum corneum of the skin to reduce trans epidermal water loss (TEWL). However, because normal water has large clusters, it is difficult to penetrate the stratum corneum of the skin. Therefore, it was considered that the use of Ultra-fine bubbles (UFB) water, which is said to have small water clusters, promotes penetration into the stratum corneum of the skin, and is useful for improving the skin barrier function. The artificial skin to which O2-UFB water was dripped had the highest water content and the lowest TEWL. It also had a high affinity for human skin. From these results, improvement of skin barrier function by O2-UFB water can be expected.

scholarly journals Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles

2017 ◽  
Vol 114 (14) ◽  
pp. 3631-3636 ◽  
Author(s):  
Robert Schulz ◽  
Kenji Yamamoto ◽  
André Klossek ◽  
Roman Flesch ◽  
Stefan Hönzke ◽  
...  
Keyword(s):  
Free Energy ◽  
Diffusion Equation ◽  
Human Skin ◽  
Barrier Function ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Drug Penetration ◽  
Energy Profiles ◽  
Long Time ◽  
Free Energy Profiles

Based on experimental concentration depth profiles of the antiinflammatory drug dexamethasone in human skin, we model the time-dependent drug penetration by the 1D general diffusion equation that accounts for spatial variations in the diffusivity and free energy. For this, we numerically invert the diffusion equation and thereby obtain the diffusivity and the free-energy profiles of the drug as a function of skin depth without further model assumptions. As the only input, drug concentration profiles derived from X-ray microscopy at three consecutive times are used. For dexamethasone, skin barrier function is shown to rely on the combination of a substantially reduced drug diffusivity in the stratum corneum (the outermost epidermal layer), dominant at short times, and a pronounced free-energy barrier at the transition from the epidermis to the dermis underneath, which determines the drug distribution in the long-time limit. Our modeling approach, which is generally applicable to all kinds of barriers and diffusors, allows us to disentangle diffusivity from free-energetic effects. Thereby we can predict short-time drug penetration, where experimental measurements are not feasible, as well as long-time permeation, where ex vivo samples deteriorate, and thus span the entire timescales of biological barrier functioning.

scholarly journals Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research

2021 ◽  
Vol 22 (2) ◽  
pp. 657
Author(s):  
Jee-Hyun Hwang ◽  
Haengdueng Jeong ◽  
Nahyun Lee ◽  
Sumin Hur ◽  
Nakyum Lee ◽  
...  
Keyword(s):  
Barrier Function ◽  
Ex Vivo ◽  
Animal Experiments ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Protective Effects ◽  
Skin Model ◽  
Porcine Skin ◽  
Single Exposure ◽  
Cosmetic Ingredients

Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1–10%), salicylic acid (0.2–2%), and lactobionic acid (1.2–12%) were used as representative substances for α-hydroxyacid (AHA), β-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50–80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.

scholarly journals Physiological Effects of Manganese Gluconate and Calcium Combination from Saint-Gervais Mont Blanc Spring Water for Human Keratinocytes Differentiation

2021 ◽  
Vol 7 (2) ◽  
pp. 1-6
Author(s):  
Franck Juchaux ◽  
Keyword(s):  
Barrier Function ◽  
Skin Barrier ◽  
Human Keratinocytes ◽  
Spring Water ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Transglutaminase 1

Alterations of skin barrier function affect quality of life and there is a need to develop dermatological/cosmetic treatments to reinforce or restore it. Inspiring of Hailey-Hailey disease, in which barrier alteration is due to a mutation of a Calcium-transporting protein (ATP2C1), we focused on the role of minerals and more especially those contained in Saint-Gervais Mont Blanc (SGMB) spring water to reinforce barrier function. Objectives: Demonstrate the interest to enrich SGMB spring water with manganese to improve both keratinocytes differentiation and barrier function. Methods: Effects of treatments on the expression of ATP2C1 and on the expression of key markers in keratinocyte differentiation and barrier function were studied by gene expression analysis on keratinocytes monolayers and also by measuring the protein expression of transglutaminase 1 using in situ immunofluorescence and image analysis in keratinocytes monolayers. Results: SGMB spring water stimulates transcriptomic expression of key markers involved in keratinocytes differentiation and barrier function while manganese gluconate has no effect. Combination of both dramatically enhances keratinocytes differentiation, in a synergistic way, at both transcriptomic and protein level. None of treatments modulated ATP2C1 expression. Conclusion: These results highlight the interest to enrich SGMB spring water with manganese to boost keratinocytes differentiation and barrier function.

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