Assessment of the Skin Barrier Function in the Reconstructed Human Epidermis using a Multimodal Approach at molecular, tissue and functional levels

The Analyst ◽  
2021 ◽  
Author(s):  
Joudi bakar ◽  
Rime Michael-Jubeli ◽  
Rindala El Khoury ◽  
Sabrina Hamla ◽  
Ali ASSI ◽  
...  
Keyword(s):  
Barrier Function ◽  
Functional Characterization ◽  
Skin Barrier ◽  
Human Epidermis ◽  
Skin Barrier Function ◽  
Multimodal Approach ◽  
Reconstructed Human Epidermis

Reconstructed human epidermis models are used as epidermis alternatives in skin researches. It is necessary to provide molecular and functional characterization in order to assess these models. Our aim is...

scholarly journals Lysates of a Probiotic, Lactobacillus rhamnosus, Can Improve Skin Barrier Function in a Reconstructed Human Epidermis Model

2019 ◽  
Vol 20 (17) ◽  
pp. 4289 ◽  
Author(s):  
Ye-On Jung ◽  
Haengdueng Jeong ◽  
Yejin Cho ◽  
Eun-Ok Lee ◽  
Hye-Won Jang ◽  
...  
Keyword(s):  
Barrier Function ◽  
Lactobacillus Rhamnosus ◽  
Skin Barrier ◽  
Human Epidermis ◽  
Skin Barrier Function ◽  
Main Function ◽  
Lauryl Sulfate ◽  
Protective Effects ◽  
Immunofluorescence Analysis ◽  
Reconstructed Human Epidermis

The main function of the skin is to protect the body from the external environment. The barrier function of the skin is mainly provided by the stratum corneum, which consists of corneocytes bound with the corneodesmosomes and lamellar lipids. Skin barrier proteins like loricrin and filaggrin also contribute to the skin barrier function. In various skin diseases, skin barrier dysfunction is a common symptom, and skin irritants like detergents or surfactants could also perturb skin barrier function. Many efforts have been made to develop strategies to improve skin barrier function. Here, we investigated whether the microfluidized lysates of Lactobacillus rhamnosus (LR), one of the most widely used probiotic species for various health benefits, may improve the skin barrier function in a reconstructed human epidermis, Keraskin™. Application of LR lysate on Keraskin™ increased the expression of tight junction proteins; claudin 1 and occludin as determined by immunofluorescence analysis, and skin barrier proteins; loricrin and filaggrin as determined by immunohistochemistry and immunofluorescence analysis and qPCR. Also, the cytotoxicity of a skin irritant, sodium lauryl sulfate (SLS), was alleviated by the pretreatment of LR lysate. The skin barrier protective effects of LR lysate could be further demonstrated by the attenuation of SLS-enhanced dye-penetration. LR lysate also attenuated the destruction of desmosomes after SLS treatment. Collectively, we demonstrated that LR lysate has protective effects on the skin barrier, which could expand the utility of probiotics to skin-moisturization ingredients.

The Role of Clindamycin Phosphate Associated with Adapalene in Three Semisolid Formulations Developed for Topical Acne Treatment

2017 ◽  
Vol 68 (5) ◽  
pp. 937-943
Author(s):  
Stela Mariana Al Hussein ◽  
Nicoleta Todoran ◽  
Silvia Imre ◽  
Hussam Al Hussein ◽  
Ana Melero Zaera ◽  
...  
Keyword(s):  
Barrier Function ◽  
Antimicrobial Agents ◽  
Acne Vulgaris ◽  
Skin Barrier ◽  
Human Epidermis ◽  
Skin Barrier Function ◽  
Clindamycin Phosphate ◽  
Oil In Water ◽  
Study Results

Despite the fact that in mild-to moderate acne vulgaris the standard first-line therapy is the topical treatment with fixed combinations of antimicrobial agents and retinoids, the skin type and the skin barrier function should be taken into account when formulating a topical product. The aim of this study was the comparison of three new semisolid formulations developed for topical application by evaluation of their rheological behavior, as well as the evaluation of in vitro percutaneous diffusion through human epidermis membrane of the pharmaceutical ingredients. Clindamycin phosphate and adapalene were incorporated in three different topical bases, an HPLC method for the determination of their content in the new formulations being developed and validated. A higher concentration of drugs was released from the two gel systems (hydroxypropylmethylcellulose 2.5% -F1 and hydroxyethylcellulose 3% -F2) than from the oil-in-water cream (F3) at pH 7.4, whereas at pH 5.5 the drugs were released in higher amounts from the formulation F3. Following the rheological behavoir associated with the penetrability through the human epidermis membrane, our study results suggest that F1 and F2 could be appropriate in treating acne lesions in patients with oily skin and unaffected skin barrier function. In contrast, the oil-in-water cream (F3), due to its possible emolient effect and its higher penetrability at pH 5.5 than gel vehicles, may be indicated for patients with dry and sensitive skin associated with an altered skin barrier.

scholarly journals Treatment with DHA Improves Epidermal Eeratinocyte Differentiation and Ameliorates Inflammation in Human Keratinocytes and Reconstructed Human Epidermis Models

2019 ◽  
Author(s):  
Tinghan Jia ◽  
Wu Qiao ◽  
Qifeng Yao ◽  
Wenhui Wu ◽  
Ken Kaku
Keyword(s):  
Topical Treatment ◽  
Barrier Function ◽  
Skin Diseases ◽  
Morphological Differentiation ◽  
Human Keratinocytes ◽  
Human Epidermis ◽  
Poly I:C ◽  
Skin Barrier Function ◽  
Mrna Levels ◽  
Reconstructed Human Epidermis

Atopic dermatitis (AD) is a chronic inflammatory skin disease, which can cause skin barrier function damaged. Although co-incubation with docosahexaenoic acid (DHA) exerts a positive effect in deficient skin model, there is no study to investigate the effects of topical treatment with DHA in inflammatory reconstructed human epidermis (RHE) model. The effects of DHA on monolayer normal human epidermal keratinocyte (NHEK) cells were evaluated via CCK-8, qPCR and ELISA. The skin related barrier function was assessed by hematoxylin-eosin (HE) staining, western blot (WB), Immunohistofluorescence (IF) and ELISA in normal and inflammatory RHE models. DHA upregulated filaggrin and loricrin expression at mRNA levels in addition to suppress overexpression of TNF-α，IL-1α and IL-6 stimulated by poly I:C plus LPS (stimulation cocktail) in cultured NHEK cells. After topical treatment with DHA, cocktail induced inflammatory characteristics of skin diseases including barrier morphological, differentiation proteins and TSLP secretion, which were alleviated in RHE models. Supplementation with DHA can improved related barrier function and have anti-inflammation effects in monolayer keratinocytes and RHE models, which indicated that DHA may have a potential value for the treatment of inflammation-associate skin diseases.

scholarly journals Treatment with Docosahexaenoic Acid Improves Epidermal Keratinocyte Differentiation and Ameliorates Inflammation in Human Keratinocytes and Reconstructed Human Epidermis Models

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3156
Author(s):  
Tinghan Jia ◽  
Wu Qiao ◽  
Qifeng Yao ◽  
Wenhui Wu ◽  
Ken Kaku
Keyword(s):  
Docosahexaenoic Acid ◽  
Topical Treatment ◽  
Barrier Function ◽  
Skin Diseases ◽  
Human Epidermis ◽  
Cell Counting ◽  
Skin Barrier Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Epidermal Keratinocyte ◽  
Reconstructed Human Epidermis

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can cause skin barrier function damage. Although co-incubation with docosahexaenoic acid (DHA) exerts a positive effect on deficient skin models, no studies have investigated the effects of topical treatment with DHA in an inflammatory reconstructed human epidermis (RHE) model. The effects of DHA on monolayer normal human epidermal keratinocyte (NHEK) cells were evaluated using cell counting kit-8 (CCK-8), real-time quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The skin-related barrier function was assessed using hematoxylin–eosin (HE) staining, Western blot (WB), immunohistofluorescence (IF), and ELISA in normal and inflammatory RHE models. Docosahexaenoic acid upregulated filaggrin and loricrin expression at mRNA levels in addition to suppressing overexpression of tumor necrosis factor-α (TNF-α), interleukin-α (IL-1α), and interleukin-6 (IL-6) stimulated by polyinosinic–polycytidylic acid (poly I:C) plus lipopolysaccharide (LPS) (stimulation cocktail) in cultured NHEK cells. After topical treatment with DHA, cocktail-induced inflammatory characteristics of skin diseases, including barrier morphology, differentiation proteins, and thymic stromal lymphopoietin (TSLP) secretion, were alleviated in RHE models. Supplementation with DHA can improve related barrier function and have anti-inflammation effects in monolayer keratinocytes and RHE models, which indicates that DHA may have potential value for the treatment of inflammation-associated skin diseases.

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 Skin Barrier Function in Psoriasis and Atopic Dermatitis: Transepidermal Water Loss and Temperature as Useful Tools to Assess Disease Severity

2021 ◽  
Vol 10 (2) ◽  
pp. 359 ◽  
Author(s):  
Trinidad Montero-Vilchez ◽  
María-Victoria Segura-Fernández-Nogueras ◽  
Isabel Pérez-Rodríguez ◽  
Miguel Soler-Gongora ◽  
Antonio Martinez-Lopez ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Water Loss ◽  
Barrier Function ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Diagnostic Tools ◽  
Psoriatic Skin ◽  
Skin Barrier Function ◽  
Healthy Controls

Multiple diagnostic tools are used to evaluate psoriasis and atopic dermatitis (AD) severity, but most of them are based on subjective components. Transepidermal water loss (TEWL) and temperature are skin barrier function parameters that can be objectively measured and could help clinicians to evaluate disease severity accurately. Thus, the aims of this study are: (1) to compare skin barrier function between healthy skin, psoriatic skin and AD skin; and (2) to assess if skin barrier function parameters could predict disease severity. A cross-sectional study was designed, and epidermal barrier function parameters were measured. The study included 314 participants: 157 healthy individuals, 92 psoriatic patients, and 65 atopic dermatitis patients. TEWL was significantly higher, while stratum corneum hydration (SCH) (8.71 vs. 38.43 vs. 44.39 Arbitrary Units (AU)) was lower at psoriatic plaques than at uninvolved psoriatic skin and healthy controls. Patients with both TEWL > 13.85 g·m−2h−1 and temperature > 30.85 °C presented a moderate/severe psoriasis (psoriasis area severity index (PASI) ≥ 7), with a specificity of 76.3%. TEWL (28.68 vs. 13.15 vs. 11.60 g·m−2 h−1) and temperature were significantly higher, while SCH (25.20 vs. 40.95 vs. 50.73 AU) was lower at AD eczematous lesions than uninvolved AD skin and healthy controls. Patients with a temperature > 31.75 °C presented a moderate/severe AD (SCORing Atopic Dermatitis (SCORAD) ≥ 37) with a sensitivity of 81.8%. In conclusion, temperature and TEWL values may help clinicians to determine disease severity and select patients who need intensive treatment.

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