Topical Application of Galgeunhwanggeumhwangryeon-Tang Recovers Skin-Lipid Barrier and Ameliorates Inflammation via Filaggrin-Thymic Stromal Lymphopoietin-Interleukin 4 Pathway

Background and objectives: The purpose of this study was to confirm the effect of Galgeunhwanggeumhwangryeon-tang (GGRT) on the skin barrier integrity and inflammation in an atopic dermatitis-like animal model. Materials and Methods: The model was established using lipid barrier elimination (LBE) in BALB/c mice. Ceramide 3B, a control drug, and GGRT were applied to the skin of LBE mice. Gross observation and histological examination were combined with measurement of skin score, trans-epidermal water loss, and pH. The expression of filaggrin, kallikrein-related peptidase 7 (KLK7), protease-activated receptor-2 (PAR-2), thymic stromal lymphopoietin (TSLP), and interleukin 4 (IL-4) was examined. Results: The effect of GGRT on atopic dermatitis was estimated in silico using two individual gene sets of human atopic dermatitis. In animal experiments, GGRT treatment reduced atopic dermatitis-like symptoms, as confirmed via gross and histological observations, skin score, pH change, and trans-epidermal water loss. The expression level of filaggrin increased in the skin of GGRT-treated mice compared to that in the LBE group. The expression levels of KLK7, PAR2, TSLP, and IL-4 were decreased in GGRT-treated mice skin compared to those in LBE mice. Conclusions: We demonstrated that GGRT restored the skin barrier and reduced inflammatory reactions in a murine model of atopic dermatitis.

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Effects of mineral complex material treatment on 2,4- dinitrochlorobenzene-induced atopic dermatitis like-skin lesions in mice model

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03259-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Johny Bajgai ◽

Jing Xingyu ◽

Ailyn Fadriquela ◽

Rahima Begum ◽

Dong Heui Kim ◽

...

Keyword(s):

Atopic Dermatitis ◽

Water Loss ◽

Immunoglobulin E ◽

Skin Barrier ◽

Skin Lesions ◽

Total Serum ◽

Skin Barrier Function ◽

Barrier Dysfunction ◽

Complex Material ◽

Mineral Complex

Abstract Background Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice. Methods Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate. Results Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups. Conclusion Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

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

Journal of Clinical Medicine ◽

10.3390/jcm10020359 ◽

2021 ◽

Vol 10 (2) ◽

pp. 359 ◽

Cited By ~ 1

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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Kallikrein 5 induces atopic dermatitis–like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome

Journal of Experimental Medicine ◽

10.1084/jem.20082242 ◽

2009 ◽

Vol 206 (5) ◽

pp. 1135-1147 ◽

Cited By ~ 322

Author(s):

Anaïs Briot ◽

Céline Deraison ◽

Matthieu Lacroix ◽

Chrystelle Bonnart ◽

Aurélie Robin ◽

...

Keyword(s):

Atopic Dermatitis ◽

Protease Inhibitor ◽

Adaptive Immune System ◽

Skin Barrier ◽

Skin Inflammation ◽

Nuclear Factor Κb ◽

Thymic Stromal Lymphopoietin ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Netherton Syndrome

Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type–related inhibitor (LEKTI). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. This skin barrier defect favors allergen absorption and is generally regarded as the underlying cause for atopy in NS. We show for the first time that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine, and the macrophage-derived chemokine are overexpressed in LEKTI-deficient epidermis. This is part of an original biological cascade in which unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2 and induces nuclear factor κB–mediated overexpression of TSLP, intercellular adhesion molecule 1, tumor necrosis factor α, and IL8. This proinflammatory and proallergic pathway is independent of the primary epithelial failure and is activated under basal conditions in NS keratinocytes. This cell-autonomous process is already established in the epidermis of Spink5−/− embryos, and the resulting proinflammatory microenvironment leads to eosinophilic and mast cell infiltration in a skin graft model in nude mice. Collectively, these data establish that uncontrolled KLK5 activity in NS epidermis can trigger atopic dermatitis (AD)–like lesions, independently of the environment and the adaptive immune system. They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy.

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Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis

Journal of Clinical Medicine ◽

10.3390/jcm9113741 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3741

Author(s):

Masutaka Furue

Keyword(s):

Atopic Dermatitis ◽

Barrier Function ◽

Coal Tar ◽

Calcineurin Inhibitors ◽

Skin Barrier ◽

Skin Inflammation ◽

Interleukin 4 ◽

Skin Barrier Function ◽

Barrier Dysfunction ◽

Therapeutic Implications

Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, the type 2 cytokines IL-4 and especially IL-13 have been indicated to have pathogenic significance in AD. Accumulating evidence has shown that the skin barrier function is regulated via competition between the aryl hydrocarbon receptor (AHR) axis (up-regulation of barrier) and the IL-13/IL-4‒JAK‒STAT6/STAT3 axis (down-regulation of barrier). This latter axis also induces oxidative stress, which exacerbates inflammation. Conventional and recently developed agents for treating AD such as steroid, calcineurin inhibitors, cyclosporine, dupilumab, and JAK inhibitors inhibit the IL-13/IL-4‒JAK‒STAT6/STAT3 axis, while older remedies such as coal tar and glyteer are antioxidative AHR agonists. In this article, I summarize the pathogenic and therapeutic implications of the IL-13/IL-4‒JAK‒STAT6/STAT3 axis and the AHR axis in AD.

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Skin barrier status during dupilumab treatment in patients with severe atopic dermatitis

Therapeutic Advances in Chronic Disease ◽

10.1177/20406223211058332 ◽

2021 ◽

Vol 12 ◽

pp. 204062232110583

Author(s):

Silvia Ferrucci ◽

Maurizio Romagnuolo ◽

Carlo Alberto Maronese ◽

Francesca Germiniasi ◽

Simona Tavecchio ◽

...

Keyword(s):

Atopic Dermatitis ◽

Skin Barrier ◽

Transepidermal Water Loss ◽

Response To Therapy ◽

Interleukin 4 ◽

Severe Atopic Dermatitis ◽

Barrier Dysfunction ◽

Relative Variation ◽

Good Tool ◽

The Status

Background: Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease hallmarked by epidermal barrier dysfunction, increased transepidermal water loss (TEWL) and decreased skin hydration. Recent findings on the T helper 2 (Th2)-driven pathogenesis of AD have led to the development of dupilumab, a monoclonal antibody directed against interleukin-4 and interleukin-13 that has been demonstrated to be effective in the treatment of moderate-to-severe AD. The effect of dupilumab on skin barrier dysfunction, however, has not yet been adequately investigated. Objectives: The primary endpoint of this study was to assess the status of the skin barrier in nonlesional skin of patients with severe AD treated with dupilumab, by evaluating the association between the relative variation of TEWL and the achievement of a 75% reduction of EASI (EASI75) over time. Methods: TEWL was measured below the antecubital fossae by means of the Vapometer® at baseline, at week 4 (T4), at week 16 (T16) and at week 32 after dupilumab starting. EASI and NRS-itch were measured at the same time points. Results: Seventy-eight patients with severe AD treated with dupilumab were enrolled. Median TEWL relative variation respect to baseline was significantly higher in patients who achieved EASI75 as compared with those who did not achieve EASI75 at T16 and at T32, but not at T4. Conclusion: During dupilumab treatment, TEWL on nonlesional skin tends to significantly improve 4 months after treatment initiation and could be a good tool for monitoring response to therapy.

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Eosinophil microRNAs Play a Regulatory Role in Allergic Diseases Included in the Atopic March

International Journal of Molecular Sciences ◽

10.3390/ijms21239011 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9011

Author(s):

Émile Bélanger ◽

Anne-Marie Madore ◽

Anne-Marie Boucher-Lafleur ◽

Marie-Michelle Simon ◽

Tony Kwan ◽

...

Keyword(s):

Allergic Rhinitis ◽

Atopic Dermatitis ◽

Immunoglobulin E ◽

Clinical Manifestations ◽

Skin Barrier ◽

Allergic Diseases ◽

Forced Expiratory Volume ◽

Inflammatory Reactions ◽

Atopic March ◽

History Of

(1) Background: The atopic march is defined by the increased prevalence of allergic diseases after atopic dermatitis onset. In fact, atopic dermatitis is believed to play an important role in allergen sensitization via the damaged skin barrier, leading to allergic diseases such as allergic asthma and allergic rhinitis. The eosinophil, a pro-inflammatory cell that contributes to epithelial damage, is one of the various cells recruited in the inflammatory reactions characterizing these diseases. Few studies were conducted on the transcriptome of this cell type and even less on their specific microRNA (miRNA) profile, which could modulate pathogenesis of allergic diseases and clinical manifestations post-transcriptionally. Actually, their implication in allergic diseases is not fully understood, but they are believed to play a role in inflammation-related patterns and epithelial cell proliferation. (2) Methods: Next-generation sequencing was performed on RNA samples from eosinophils of individuals with atopic dermatitis, atopy, allergic rhinitis and asthma to obtain differential counts of primary miRNA (pri-miRNA); these were also analyzed for asthma-related phenotypes such as forced expiratory volume in one second (FEV1), immunoglobulin E (IgE) and provocative concentration of methacholine inducing a 20% fall in forced expiratory volume in 1 s (PC20) levels, as well as FEV1 to forced vital capacity (FEV1/FVC) ratio. (3) Results: Eighteen miRNAs from eosinophils were identified to be significantly different between affected individuals and unaffected ones. Based on counts from these miRNAs, individuals were then clustered into groups using Ward’s method on Euclidian distances. Groups were found to be explained by asthma diagnosis, familial history of respiratory diseases and allergic rhinitis as well as neutrophil counts. (4) Conclusions: The 18 differential miRNA counts for the studying phenotypes allow a better understanding of the epigenetic mechanisms underlying the development of the allergic diseases included in the atopic march.

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Effect of Topically Applied Wikstroemia dolichantha Diels on the Development of Atopic Dermatitis-Like Skin Symptoms in Mice

Nutrients ◽

10.3390/nu11040914 ◽

2019 ◽

Vol 11 (4) ◽

pp. 914 ◽

Cited By ~ 1

Author(s):

Jonghwan Jegal ◽

No-June Park ◽

Tae-Young Kim ◽

Sangho Choi ◽

Sang Woo Lee ◽

...

Keyword(s):

Atopic Dermatitis ◽

Barrier Function ◽

Immunoglobulin E ◽

Skin Barrier ◽

Skin Lesions ◽

Transepidermal Water Loss ◽

Skin Hydration ◽

Interleukin 4 ◽

Skin Barrier Function ◽

Skin Symptoms

Plants of the genus Wikstroemia are traditionally used to treat inflammatory diseases like bronchitis and rheumatoid arthritis. In the present study, the anti-atopic effects of an EtOH extract of Wikstroemia dolichantha (WDE) on oxazolone- and DNCB (2,4-dinitrochlorobenzene)-induced dermatitis in mice were investigated. Both ears of BALB/c mice were exposed to oxazolone, and dorsal skins of SKH-1 hairless mice were sensitized with DNCB to induce acute eczematous atopic skin lesions. 1% WDE was applied daily to oxazolone- and DNCB-induced AD mice for two or three weeks, respectively. Total IL-4 and IgE concentrations in serum, transepidermal water loss (TEWL) and skin hydration were assessed. High-performance liquid chromatography/mass spectrometry (HPLC/MS) was used to determine the composition of WDE. Dermal application of 1% WDE grossly and histopathologically improved oxazolone- and DNCB-induced AD skin symptoms. Epidermal thickness and mast cell infiltration were significantly lower in animals treated with WDE than in vehicle controls. Furthermore, in addition to reducing DNCB-induced increases in serum IL-4 (interleukin 4) and IgE (immunoglobulin E) levels, WDE also decreased TEWL and increased skin hydration (indicative of improved skin barrier function). The four flavonoids taxifolin, aromadendrin, padmatin and chamaejasmine were tentatively identified in WDE by HPLC-DAD/QTOF-MS. The above results show WDE protected against oxazolone- and DNCB-induced AD in mice by down-regulating the TH2-associated cytokine IL-4 and improving skin barrier function and suggest WDE might be useful for the management of atopic dermatitis.

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Faculty Opinions recommendation of Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725326253.793504346 ◽

2015 ◽

Author(s):

Hywel Williams

Keyword(s):

Atopic Dermatitis ◽

Water Loss ◽

Skin Barrier ◽

Transepidermal Water Loss ◽

Barrier Dysfunction

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Echinochrome A Treatment Alleviates Atopic Dermatitis-like Skin Lesions in NC/Nga Mice via IL-4 and IL-13 Suppression

Marine Drugs ◽

10.3390/md19110622 ◽

2021 ◽

Vol 19 (11) ◽

pp. 622

Author(s):

Hyeong Rok Yun ◽

Sang Woo Ahn ◽

Bomin Seol ◽

Elena A. Vasileva ◽

Natalia P. Mishchenko ◽

...

Keyword(s):

Atopic Dermatitis ◽

Clinical Symptoms ◽

Sea Urchins ◽

Skin Barrier ◽

Skin Lesions ◽

Transepidermal Water Loss ◽

Interleukin 4 ◽

Barrier Dysfunction ◽

Echinochrome A ◽

Anti Inflammatory

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to dryness, pruritus, and erythematous lesions. AD is triggered by immune imbalance and oxidative stress. Echinochrome A (Ech A), a natural pigment isolated from sea urchins, exerts antioxidant and beneficial effects in various inflammatory disease models. In the present study, we tested whether Ech A treatment alleviated AD-like skin lesions. We examined the anti-inflammatory effect of Ech A on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions in an NC/Nga mouse model. AD-like skin symptoms were induced by treatment with 1% DNCB for 1 week and 0.4% DNCB for 5 weeks in NC/Nga mice. The results showed that Ech A alleviated AD clinical symptoms, such as edema, erythema, and dryness. Treatment with Ech A induced the recovery of epidermis skin lesions as observed histologically. Tewameter® and Corneometer® measurements indicated that Ech A treatment reduced transepidermal water loss and improved stratum corneum hydration, respectively. Ech A treatment also inhibited inflammatory-response-induced mast cell infiltration in AD-like skin lesions and suppressed the expression of proinflammatory cytokines, such as interferon-γ, interleukin-4, and interleukin-13. Collectively, these results suggest that Ech A may be beneficial for treating AD owing to its anti-inflammatory effects.

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