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 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 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 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 IgE Autoreactivity in Atopic Dermatitis: Paving the Road for Autoimmune Diseases?

Antibodies ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 47
Author(s):  
Christophe Pellefigues
Keyword(s):  
Atopic Dermatitis ◽  
Autoimmune Diseases ◽  
Current Knowledge ◽  
Skin Barrier ◽  
Allergic Diseases ◽  
Specific Ige ◽  
Barrier Dysfunction ◽  
The Road ◽  
Common Skin ◽  
Chronic Skin

Atopic dermatitis (AD) is a common skin disease affecting 20% of the population beginning usually before one year of age. It is associated with the emergence of allergen-specific IgE, but also with autoreactive IgE, whose function remain elusive. This review discusses current knowledge relevant to the mechanisms, which leads to the secretion of autoreactive IgE and to the potential function of these antibodies in AD. Multiple autoantigens have been described to elicit an IgE-dependent response in this context. This IgE autoimmunity starts in infancy and is associated with disease severity. Furthermore, the overall prevalence of autoreactive IgE to multiple auto-antigens is high in AD patients. IgE-antigen complexes can promote a facilitated antigen presentation, a skewing of the adaptive response toward type 2 immunity, and a chronic skin barrier dysfunction and inflammation in patients or AD models. In AD, skin barrier defects and the atopic immune environment facilitate allergen sensitization and the development of other IgE-mediated allergic diseases in a process called the atopic march. AD is also associated epidemiologically with several autoimmune diseases showing autoreactive IgE secretion. Thus, a potential outcome of IgE autoreactivity in AD could be the development of further autoimmune diseases.

scholarly journals The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

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.

scholarly journals Treatment of atopic dermatitis using non-thermal atmospheric plasma in an animal model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ik Jun Moon ◽  
Mi Ra Yun ◽  
Hae Kyeong Yoon ◽  
Keon Hee Lee ◽  
Sun Young Choi ◽  
...  
Keyword(s):  
Animal Model ◽  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Treated Group ◽  
Transepidermal Water Loss ◽  
Atmospheric Plasma ◽  
Therapeutic Modality ◽  
Skin Barrier Function ◽  
Control Group ◽  
Epidermal Thickness

AbstractCold atmospheric plasma (CAP) has been incorporated into various fields, including promotion of cutaneous wound healing. Atopic dermatitis (AD) is a chronic cutaneous condition characterized by inflammation-induced skin wounds and impaired skin barrier function. To investigate whether CAP may improve AD using an animal model. Dermatophagoides farinae extracts (DFE)-induced murine models of AD were used in this study. The plasma-treated group received a total of 6 CAP treatments during 2 weeks, while the control group did not receive any treatment. Differences in dermatitis severity, transepidermal water loss (TEWL), serum level of immunoglobulin (Ig) E and epidermal thickness were evaluated in both groups. The dermatitis severity was significantly improved by CAP treatment. TEWL was lower in the plasma-treated group compared with the non-treated control group. Serum Ig E dropped significantly after treatment with CAP. Difference in epidermal thickness of the ear skin was not significant between the plasma-treated and non-treated groups. Localized treatment of AD with CAP decreases dermatitis severity, TEWL, and serum Ig E level. These results show CAP’s potentials as a novel therapeutic modality for AD.

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