scholarly journals Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1237
Author(s):  
Thomas Bauer ◽  
Daniela Gubi ◽  
Jörg Klufa ◽  
Philipp Novoszel ◽  
Martin Holcmann ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
The Body ◽  
Suitable Model ◽  
Ex Vivo Model ◽  
Egfr Inhibition ◽  
Explant Cultures ◽  
Barrier Immunity

The skin is the outermost barrier protecting the body from pathogenic invasion and environmental insults. Its breakdown initiates the start of skin inflammation. The epidermal growth factor (EGFR) on keratinocytes protects this barrier, and its dysfunction leads to atopic dermatitis-like skin disease. One of the initial cytokines expressed upon skin barrier breach and during atopic dermatitis is TSLP. Here, we describe the expression and secretion of TSLP during EGFR inhibition and present an ex-vivo model, which mimics the early events after barrier insult. Skin explants floated on culture medium at 32 °C released TSLP in parallel to the activation of the resident Langerhans cell network. We could further show the up-regulation and activation of the AP-1 family of transcription factors during atopic-like skin inflammation and its involvement in TSLP production from the skin explant cultures. Inhibition of the c-Jun N-terminal kinase pathway led to a dose-dependent blunting of TSLP release. These data indicate the involvement of AP-1 during the early stages of atopic-like skin inflammation and highlight a novel therapeutic approach by targeting it. Therefore, skin explant cultures mimic the early events during skin barrier immunity and provide a suitable model to test therapeutic intervention.

scholarly journals Topical Pioglitazone Nanoformulation for the Treatment of Atopic Dermatitis: Design, Characterization and Efficacy in Hairless Mouse Model

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 255 ◽  
Author(s):  
Lupe Carolina Espinoza ◽  
Rodrigo Vera-García ◽  
Marcelle Silva-Abreu ◽  
Òscar Domènech ◽  
Josefa Badia ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Skin Barrier ◽  
Inflammatory Cells ◽  
Hairless Mouse ◽  
Skin Barrier Function ◽  
Inflammatory Parameters ◽  
Therapeutic Benefits

Pioglitazone (PGZ) is a drug used to treat type 2 diabetes mellitus that has been reported to show additional therapeutic activities on diverse inflammatory parameters. The aim of this study was to optimize a topical PGZ-loaded nanoemulsion (PGZ-NE) in order to evaluate its effectiveness for treating atopic dermatitis (AD). The composition of the nanoformulation was established by pseudo-ternary diagram. Parameters such as physical properties, stability, in vitro release profile, and ex vivo permeation were determined. The efficacy study was carried out using oxazolone-induced AD model in hairless mice. PGZ-NE released the drug following a hyperbolic kinetic. Additionally, its properties provided high retention potential of drug inside the skin. Therapeutic benefits of PGZ-NE were confirmed on diverse events of the inflammatory process, such as reduction of lesions, enhancement of skin barrier function, diminished infiltration of inflammatory cells, and expression of pro-inflammatory cytokines. These results were reinforced by atomic force microscope (AFM), which demonstrated the ability of the formulation to revert the rigidification caused by oxazolone and consequently improve the elasticity of the skin. These results suggest that PGZ-NE may be a promising treatment for inflammatory dermatological conditions such as AD.

scholarly journals Bacterial skin colonization and infections in patients with atopic dermatitis

2012 ◽  
Vol 87 (5) ◽  
pp. 729-734 ◽  
Author(s):  
Vanessa Petry ◽  
Giancarlo Resende Bessa ◽  
Claudia Schermann Poziomczyck ◽  
Caio Fernando de Oliveira ◽  
Magda Blessmann Weber ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Secondary Infection ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Skin Surface ◽  
Number Of Children ◽  
Chronic Skin ◽  
Systemic Antibiotics

Atopic Dermatitis is a chronic inflammatory skin disease that affects a large number of children and adults. The disease results from an interaction between genetic predisposition, host environment, skin barrier defects, and immunological factors. A major aggravating factor associated with Atopic Dermatitis is the presence of microorganisms on the patient's skin surface. Staphylococcus aureus and Streptococcus pyogenes, for instance, can exacerbate chronic skin inflammation. As a result, antimicrobials have often been prescribed to control the acute phase of the disease. However, increased bacterial resistance to antimicrobial agents has made it difficult for dermatologists to prescribe appropriate medication. In the presence of disseminated dermatitis with secondary infection, systemic antibiotics need to be prescribed; however, treatment should be individualized, in an attempt to find the most effective antibiotic with fewer side effects. Also, the medication should be used for as short as possible in order to minimize bacterial resistance.

scholarly journals Stress and Skin: An Overview of Mind Body Therapies as a Treatment Strategy in Dermatology

2021 ◽  
pp. e2021091
Author(s):  
Rachel Graubard ◽  
Ariadna Perez-Sanchez ◽  
Rajani Katta
Keyword(s):  
Stress Response ◽  
Skin Disease ◽  
Skin Barrier ◽  
Psychosocial Outcomes ◽  
Skin Inflammation ◽  
The Body ◽  
Skin Barrier Function ◽  
Beneficial Effects ◽  
Potential Benefits ◽  
The Mind

Stress has multiple and wide-ranging physiologic and clinical impacts on skin disease. This has led to an interest in mind body therapies as potential adjunct treatments for skin disease. The stress response results in the activation of the endocrine, neurologic, and immune systems, with a resulting cascade of impacts, that are both systemic and cutaneous. The 2 main arms of the stress response are the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. The resultant release of cortisol, catecholamines, and neuropeptides has multiple effects. Clinically, these have been shown to increase skin inflammation, increase itching, impair skin barrier function, impair wound healing, and suppress immunity.Mind body therapies are those that focus on the interaction between the mind and the body, with the goal to influence physical function and impact health. These have been shown to ameliorate some of the harmful physiologic changes attributed to stress or to reduce harmful behaviors. In some cases, such as with biofeedback, they may also result in beneficial physiologic changes. Treatments such as meditation, biofeedback, hypnosis, guided imagery, and others have been evaluated in the treatment of skin disease and have shown some benefits. Although randomized controlled trials are limited, these interventions have shown beneficial effects on itching, psychosocial outcomes, and even skin severity. These interventions have been evaluated in diseases such as atopic dermatitis, psoriasis, trichotillomania, and others. Given the potential benefits, improvements in psychosocial outcomes, and a low risk profile, referral to qualified practitioners or multidisciplinary clinics should be considered for some patients.

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

2009 ◽  
Vol 206 (5) ◽  
pp. 1135-1147 ◽  
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.

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.

Severe skin inflammation and filaggrin mutation similarly alter the skin barrier in patients with atopic dermatitis

2014 ◽  
Vol 170 (3) ◽  
pp. 617-624 ◽  
Author(s):  
G. Mócsai ◽  
K. Gáspár ◽  
G. Nagy ◽  
B. Irinyi ◽  
A. Kapitány ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Skin Inflammation

scholarly journals Food allergy and atopic dermatitis

2020 ◽  
Vol 2 (1) ◽  
pp. 35-38
Author(s):  
Tina Banzon ◽  
Donald Y.M. Leung ◽  
Lynda C. Schneider
Keyword(s):  
Atopic Dermatitis ◽  
Food Allergy ◽  
Immunoglobulin E ◽  
Growth Failure ◽  
Skin Barrier ◽  
Clinical History ◽  
Skin Inflammation ◽  
Specific Ige ◽  
Nutritional Deficiencies ◽  
Detailed Clinical History

Atopic dermatitis (AD), characterized by intense pruritus, eczematous lesions, and a relapsing disease course, is a chronic inflammatory skin disease that affects both children and adults. AD often begins in infancy and is associated with atopic diseases in the personal or family history.1 Environmental factors may trigger AD by affecting the skin barrier and by triggering inflammation. The elicitation of T-helper type 2 cytokines further impairs the epidermal barrier and leads to the penetration of irritants and allergens into the epidermis and thereby perpetuating inflammation. The presence of AD and its severity has been shown to positively correlate with risk of developing food allergy (FA). Children with AD are estimated to be six times more likely to develop FA compared with their healthy peers. It has been reported that nearly 40% of children with moderate-to-severe AD have immunoglobulin E (IgE) mediated FA compared with only 6% in the general population. Although analysis of experimental data has linked skin inflammation in AD to FA, with food challenges reproducing symptoms and avoidance diets improving AD, elimination diets are not known to cure AD and may have unfavorable consequences, such as loss of tolerance, which leads to immediate-type allergy, including anaphylaxis, nutritional deficiencies, growth failure, and reduction of quality of life for the patient and family. Exacerbation of AD can be inaccurately attributed to foods. Individuals with AD are often sensitized to foods with positive testing results, however, able to tolerate the food. In light of widespread ordering and commercial availability of serum specific IgE for FA, testing for FA is recommended only if, from a detailed clinical history, immediate-type allergic symptoms occur with ingestion of food, or in infants with AD who do not improve with optimal skin care.

The Comparative Efficacy Between Shea Butter-Ceramide Cream and 1% Hydrocortisone Cream in Childhood Atopic Dermatitis

2021 ◽  
Vol 104 (7) ◽  
pp. 1172-1178
Keyword(s):  
Atopic Dermatitis ◽  
Adverse Events ◽  
Median Time ◽  
Skin Barrier ◽  
The Body ◽  
Shea Butter ◽  
Skin Barrier Function ◽  
Double Blind Study ◽  
Butyrospermum Parkii ◽  
Time To Relapse

Background: Atopic dermatitis (AD) is the most common chronic eczema in children due to skin barrier dysfunction. Topical non-steroidal antiinflammatory agents such as Butyrospermum parkii (shea butter) and ceramide are developed to target specific defects in skin barrier function in AD patients and to reduce the side effects of topical corticosteroids. Objective: To compare the efficacy of the emollient containing shea butter and ceramide to 1% hydrocortisone in childhood AD. Materials and Methods: The present study was a randomized, double-blind study in 26 children, aged 2 to 18 years, with mild to moderate AD. The patients were randomized to treat twice daily with shea butter and ceramide cream (SC) on one side of the body and 1% hydrocortisone on the other side. The treatment period was eight weeks, with follow-ups on the second, fourth, sixth, and eighth week. The shea butter and ceramide side were applied for eight weeks; while the 1% hydrocortisone side was applied for the first four weeks and changed to cream base for the latter four weeks. The clinical outcomes were evaluated by using SCORAD and POEM at baseline, and on every follow up week. Time to remission, time to relapse, and adverse events were evaluated. Results: The result showed a significant improvement of SCORAD and POEM in both groups after eight weeks of treatment. When comparing the two groups, it was found that SCORAD and POEM were not different. Regarding the median time to remission and the median time to relapse, there was no statistical difference between the two groups of treatments. There were no related adverse events. Conclusion: The emollient containing shea butter and ceramide is effective in the treatment and prevention of relapse in childhood mild to moderate atopic dermatitis. Keywords: Ceramide; Butyrospermum parkii; shea butter; atopic dermatitis

scholarly journals Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section IV: Treatment Options for the Management of Atopic Dermatitis

2018 ◽  
Vol 22 (1_suppl) ◽  
pp. 21S-29S ◽  
Author(s):  
Gurbir Dhadwal ◽  
Lorne Albrecht ◽  
Robert Gniadecki ◽  
Yves Poulin ◽  
Jensen Yeung ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Topical Therapy ◽  
Treatment Options ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Skin Barrier Function ◽  
Improve Quality ◽  
Consensus Document ◽  
Basic Care

The objectives of therapy for atopic dermatitis (AD) are to reduce skin inflammation and pruritus, restore skin barrier function, and improve quality of life (QoL). Treatments can be classified as moisturizing and basic care, topical therapy, phototherapy, and systemic therapy. In this review, we summarize the treatments for AD and recommendations for their use.

scholarly journals Trends in Atopic Dermatitis—From Standard Pharmacotherapy to Novel Drug Delivery Systems

2019 ◽  
Vol 20 (22) ◽  
pp. 5659 ◽  
Author(s):  
Eliana B. Souto ◽  
João Dias-Ferreira ◽  
Jéssica Oliveira ◽  
Elena Sanchez-Lopez ◽  
Ana Lopez-Machado ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Atopic Dermatitis ◽  
Drug Delivery Systems ◽  
Calcineurin Inhibitors ◽  
Skin Barrier ◽  
Delivery Systems ◽  
The Body ◽  
Barrier Dysfunction ◽  
First Line Therapy ◽  
Skin Delivery

Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by robust burning and eczematous lacerations in diverse portions of the body. AD affects about 20% of both offspring and adults worldwide. The pathophysiology of AD combines environmental, hereditary, and immunological aspects, together with skin barrier dysfunction. The procedures used to prevent the disease are the everyday usage of creams to support the restoration of the epidermal barrier. The classical treatments include the use of topical corticosteroids as a first-line therapy, but also calcineurin inhibitors, antihistamines, antibiotics, phototherapy, and also immunosuppressant drugs in severe cases of AD. Topical drug delivery to deeper skin layers is a difficult task due to the skin anatomic barrier, which limits deeper penetration of drugs. Groundbreaking drug delivery systems, based on nanoparticles (NPs), have received much attention due to their ability to improve solubility, bioavailability, diffusion, targeting to specific types of cells, and limiting the secondary effects of the drugs employed in the treatment of AD. Even so, additional studies are still required to recognize the toxicological characteristics and long-term safety of NPs. This review discusses the current classical pharmacotherapy of AD against new nanoparticle skin delivery systems and their toxicologic risks.

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