scholarly journals 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

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.

scholarly journals Deacetylasperulosidic Acid Ameliorates Pruritus, Immune Imbalance, and Skin Barrier Dysfunction in 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis NC/Nga Mice

2021 ◽  
Vol 23 (1) ◽  
pp. 226
Author(s):  
Jin-Su Oh ◽  
Geum-Su Seong ◽  
Yong-Deok Kim ◽  
Se-Young Choung
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Barrier Function ◽  
Skin Barrier ◽  
Inflammatory Cells ◽  
Inflammatory Factors ◽  
Skin Barrier Function ◽  
Barrier Dysfunction ◽  
Immune Balance ◽  
Immune Imbalance

The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1β, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.

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

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 914 ◽  
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.

scholarly journals The Pathogenic and Therapeutic Implications of Ceramide Abnormalities in Atopic Dermatitis

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2386
Author(s):  
Masanori Fujii
Keyword(s):  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Permeability Barrier ◽  
Barrier Dysfunction ◽  
Therapeutic Implications ◽  
Beneficial Effects ◽  
Chronic Skin ◽  
Th1 Cytokines ◽  
Lipid Abnormalities

Ceramides play an essential role in forming a permeability barrier in the skin. Atopic dermatitis (AD) is a common chronic skin disease associated with skin barrier dysfunction and immunological abnormalities. In patients with AD, the amount and composition of ceramides in the stratum corneum are altered. This suggests that ceramide abnormalities are involved in the pathogenesis of AD. The mechanism underlying lipid abnormalities in AD has not yet been fully elucidated, but the involvement of Th2 and Th1 cytokines is implicated. Ceramide-dominant emollients have beneficial effects on skin barrier function; thus, they have been approved as an adjunctive barrier repair agent for AD. This review summarizes the current understanding of the mechanisms of ceramide abnormalities in AD. Furthermore, the potential therapeutic approaches for correcting ceramide abnormalities in AD are discussed.

scholarly journals Role of AHR Ligands in Skin Homeostasis and Cutaneous Inflammation

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3176
Author(s):  
Nieves Fernández-Gallego ◽  
Francisco Sánchez-Madrid ◽  
Danay Cibrian
Keyword(s):  
Atopic Dermatitis ◽  
Barrier Function ◽  
Inflammatory Responses ◽  
Normal Skin ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
In Vitro Assays ◽  
Skin Barrier Function

Aryl hydrocarbon receptor (AHR) is an important regulator of skin barrier function. It also controls immune-mediated skin responses. The AHR modulates various physiological functions by acting as a sensor that mediates environment–cell interactions, particularly during immune and inflammatory responses. Diverse experimental systems have been used to assess the AHR’s role in skin inflammation, including in vitro assays of keratinocyte stimulation and murine models of psoriasis and atopic dermatitis. Similar approaches have addressed the role of AHR ligands, e.g., TCDD, FICZ, and microbiota-derived metabolites, in skin homeostasis and pathology. Tapinarof is a novel AHR-modulating agent that inhibits skin inflammation and enhances skin barrier function. The topical application of tapinarof is being evaluated in clinical trials to treat psoriasis and atopic dermatitis. In the present review, we summarize the effects of natural and synthetic AHR ligands in keratinocytes and inflammatory cells, and their relevance in normal skin homeostasis and cutaneous inflammatory diseases.

scholarly journals The efficacy and safety of local therapy of atopic dermatitis in infants and school-age children

2020 ◽  
pp. 54-59
Author(s):  
O. I. Sidorovich ◽  
A. A. Tsyvkina ◽  
G. D. Abdullaeva
Keyword(s):  
Atopic Dermatitis ◽  
Local Therapy ◽  
Calcineurin Inhibitors ◽  
Skin Inflammation ◽  
School Age Children ◽  
Skin Barrier Function ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Atopic March ◽  
Age Related

Atopic dermatitis is a multifactorial genetic inflammatory skin disease associated with disturbances of skin barrier function affected by predisposition to IgE-mediated hypersensitivity, which is characterized by itching, chronic recurrent course of the disease, age-related features of localization and lesion morphology, and requires the long-term and permanent treatment.Treatment is based on the continuous use of emollients, topical calcineurin inhibitors, topical glucocorticoids, and hygienic skin care.The mechanisms of the atopic dermatitis development are primarily based on a genetic predisposition to allergies, failure of the normal development of congenital and acquired factors of the immune system, as well as the influence of environmental factors and various trigger factors, such as allergenic (food, indoor, epidermal, fungal allergens, etc.). and non-allergenic (tobacco smoke, pollutants, psycho-emotional stress, concomitant chronic and acute diseases, mainly ARVI, etc.).It has been established that atopic dermatitis is characterized by the epidermal barrier dysfunction leading to excessive tran-sepidermal water loss, increased permeability of the epidermis, the penetration of allergens and microbial agents via the skin and eventually to sensitization to allergens and the development of specific allergic skin inflammation and atopic march with the sequential development of other atopic diseases.Modern therapeutic strategies are actively aimed at repairing the epidermal barrier, preventing sensitization and atopic march development. This article describes the features of the epidermal barrier dysfunction in atopic dermatitis, lists the methods of its restoration and ways to prevent subsequent exacerbations using local therapy and emollients, and presents 3 clinical cases.

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

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.

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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