Role In Atopic Dermatitis Research Articles

341 IL-4Rα Targeted-POLIGOTM Cream Improves DNCB-Induced Atopic Dermatitis Mouse Model

Atopic dermatitis (AD) is the most common type of eczema. The Th2 immune response seems to play a pivotal role in AD. This involves in Th2 cytokines such as IL-4 which share the IL-4Rα. Transdermal administration improves patient quality of life because of noninvasive; however, typical ASO and antibody drug delivery into the skin can be challenging owing to the barrier of tight junctions in the granular layer. Therefore, we aimed to develop a delivery system of ASO for topical application using our technology, POLIGOTM. POLIGOTM, which is based on PNA (Peptide Nucleic Acid) has the nanoparticle characters and is able to transdermal delivery without physical force (microneedle). We improved the PNA (high selectivity, stability, nanoparticle-characters) to overcome low selectivity and delivery using our technology. Our purpose was to evaluate the effects of POL201 (cream type of IL-4Rα targeted POLIGOTM) on dinitrochlorobenzene (DNCB) induced NC/Nga mice. We measured epidermis thickness, CD3, and CD11c expression of DNCB-induced AD mouse skin and the levels of IgE, IL-4, IL-13, and TARC in the serum by ELISA. Also, the effects of POL201 on expression level of IL-4Rα was evaluated in AD mouse skin. POL201 efficiently decreased the number of CD3/CD11c positive cells as well as thickness of the epidermis and dermis. The POL201 group significantly reduced serum level of IgE, IL-4, IL-13 and TARC. Moreover, IL-4Rα inhibited in the POL201 group compared with the DNCB-treated group. In addition, POL201 group showed that the clinical index, SCORAD (redness, scabs, itching and thickness) was dramatically improved than positive control (dexamethasone group). As the results, POL201 significantly inhibited AD pathogenesis and clinical index through reduction of IL-4Rα expression in AD animal model. Unlike conventional ASO treatments (subcutaneous injection), POL201 was able to deliver to the skin using cream formulation alone and inhibited the target gene IL-4Rα. Our results suggest that POL201 could be a potential therapeutic candidate for the treatment of AD.

Decreased expression of suprabasin induces aberrant differentiation and apoptosis of epidermal keratinocytes: Possible role for atopic dermatitis

BackgroundSuprabasin (SBSN), a secreted protein, is expressed in various epithelial tissues. The role of SBSN in epidermal differentiation and atopic dermatitis (AD) pathology remains largely unknown. ObjectiveTo evaluate the effects of SBSN on epidermal keratinocytes and its role in AD. MethodsWe examined the SBSN expression levels in the stratum corneum and the epidermis by proteome analysis and immunohistochemistry, respectively. The serum SBSN concentration was measured by ELISA. These values were compared between AD and healthy control. Morphological changes in the epidermis were investigated in SBSN-knockdown three-dimensional human living skin equivalent (LSE) model with or without IL-4/IL-13. ResultsEpidermal SBSN expression was decreased in AD lesional skin compared to healthy skin, as assessed by the stratum corneum proteome analysis and immunohistochemistry. The SBSN serum levels were significantly lower in AD patients than in normal subjects (P<0.05). The SBSN-deficient LSE exhibited compact stratum corneum, immature stratum granulosum, and increased keratinocyte apoptosis. Th2 cytokines, IL-4 and IL-13, did not affect SBSN expression in LSE. There were no differentiation-associated makers that were affected by the SBSN knockdown. SBSN deficiency-induced apoptosis of keratinocytes was exaggerated by IL-4/IL-13, and accordingly, the addition of recombinant SBSN induced significant keratinocyte proliferation (P<0.05). ConclusionOur data demonstrated that SBSN regulates normal epidermal barrier. Th2 cytokines unaffect SBSN expression in keratinocytes, but promote SBSN deficiency-induced apoptosis. It is suggested that SBSN has an anti-apoptotic activity, and its deficiency is involved in the pathogenesis of AD.

Insight into the redox status of inflammatory skin equivalents as determined by EPR spectroscopy

Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis is still not fully understood. Since inflammatory processes correlate with oxidative stress, the redox status may play a key role in AD. In this study, electron paramagnetic resonance (EPR) spectroscopy was mainly used to investigate the redox status in normal and inflammatory skin equivalents mimicking characteristics of AD in vitro using EPR spin probes (TEMPO, PCA) and a spin trap (DMPO). The total antioxidant status in the hydrophilic and lipophilic compartments of skin (microenvironment) showed no differences between the skin equivalents. In the inflammatory skin equivalents, a decreased glutathione concentration in the epidermis and an increased metabolic radical production could be observed compared to normal skin equivalents. The induction of external stress by simulated solar irradiation (UVB-NIR) resulted in the same amount and type of radicals in normal and inflammatory skin equivalents. For the first time, the antioxidant and oxidant status of inflammatory in vitro skin equivalents was analyzed by EPR to elucidate their redox status using different methods which focus on various microenvironments. Our investigations suggested that the redox status in atopic skin could be different, but this should be investigated more comprehensively, because the results can vary depending on the used methods and where the investigations take place.

Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation.

Hedgehog (Hh) proteins regulate development and tissue homeostasis, but their role in atopic dermatitis (AD) remains unknown. We found that on induction of mouse AD, Sonic Hedgehog (Shh) expression in skin and Hh pathway action in skin T cells were increased. Shh signaling reduced AD pathology and the levels of Shh expression determined disease severity. Hh-mediated transcription in skin T cells in AD-induced mice increased Treg populations and their suppressive function through increased active transforming growth factor–β (TGF-β) in Treg signaling to skin T effector populations to reduce disease progression and pathology. RNA sequencing of skin CD4+ T cells from AD-induced mice demonstrated that Hh signaling increased expression of immunoregulatory genes and reduced expression of inflammatory and chemokine genes. Addition of recombinant Shh to cultures of naive human CD4+ T cells in iTreg culture conditions increased FOXP3 expression. Our findings establish an important role for Shh upregulation in preventing AD, by increased Gli-driven, Treg cell–mediated immune suppression, paving the way for a potential new therapeutic strategy.

Update on protease-activated receptor 2 in cutaneous barrier, differentiation, tumorigenesis and pigmentation, and its role in related dermatologic diseases.

Protease-activated receptor 2 (PAR2) is a transmembrane receptor expressed by multiple tissues, including skin, with rapidly expanding knowledge regarding its roles. In the skin, PAR2 has extensively documented effects in promoting Th2 inflammation and pruritus; and its role in atopic dermatitis continues to be thoroughly studied. Numerous new investigations have shown a more complex range of activities potentially related to dermatologic diseases. Goal of this review is to outline emerging effects of PAR2 activation in the skin other than those related to immunologic and pruritic functions. Specifically, this work seeks to summarize current knowledge (and gaps) of PAR2 as a regulator of epidermal barrier, keratinocyte differentiation, cutaneous tumorigenesis and pigmentation. Additional focus will be placed on possible involvement in dermatologic disease and emergence as a therapeutic target.

Urinary leukotriene e4 level profile in various degrees of severity in atopic dermatitis patients in dermatovenereology outpatient clinic Dr. Soetomo General Hospital, Surabaya: A descriptive study

Atopic dermatitis (AD) is a chronic, relapsing skin inflammatory disease. Corticosteroid as the cornerstone treatment for AD has some flaw, especially for the chronic recalcitrant AD, since it has side effects and high possibility of rebound. Leukotriene receptor antagonist (LTRA) which has been used for asthma and allergic rhinitis now has been developed for treating AD, based on the similar mechanism of inflammation. Leukotriene (LT) is an inflammatory mediator that is thought to play role in the asthma, allergic rhinitis, and AD. Urinary leukotriene E4 (U-LTE4), the stable metabolite of LT, can be found in urine. This research aims to evaluate the role of LT in various degrees of severity in AD patients by measuring U-LTE4 levels using Enzyme Linked Immunosorbent Assay (ELISA). Twenty two AD patients who were in a flare state and came to the outpatient clinic on April – July 2017 were measured their U-LTE4 levels. The results demonstrated that mean of U-LTE4 levels increases consistently with intensity of the degree of severity, and this finding supports previous study that LT plays role in AD.

Micronutrients in Atopic Dermatitis: A Systematic Review.

Objective: The pathophysiology of atopic dermatitis (AD) involves a complex interplay between immune system dysfunction, genetics, and environmental factors. It is well known that nutritional status is essential to a proper functioning immune system, leading to a highly debated question regarding the role of dietary factors in the pathogenesis of AD. Food allergies and elimination diets have been broadly studied in atopy; however, less consideration has been given to how vitamins, minerals, and other micronutrients influence the risk for AD and severity of symptoms. This systematic review discusses evidence on how various micronutrients, including vitamins (C, E, and D) and trace minerals (zinc, selenium, iron, copper, magnesium, and strontium) are associated with AD, and how supplementation influence disease severity. Design: A systematic search was conducted to identify the role that oral micronutrients have on AD. The authors reviewed 49 studies herein. Results: While there are weak associations between vitamins C or E and AD, there is sufficient evidence to suggest that vitamin D supplementation provides benefit in AD patients. Deficiency of selenium and zinc may exacerbate AD. Current reports are not sufficient to confidently discern the role of other vitamins and trace minerals on AD. Conclusions: Though oral micronutrients may play a role in AD, the current literature is limited, and there is a need for more comprehensive randomized controlled trials (RCTs) to truly decipher the role between oral micronutrients and AD.

Neuroplastin-β mediates S100A8/A9-induced lung cancer disseminative progression.

Compiling evidence indicates an unusual role of extracellular S100A8/A9 in cancer metastasis. S100A8/A9 secreted from either cancer cells or normal cells including epithelial and inflammatory cells stimulates cancer cells through S100A8/A9 sensor receptors in an autocrine or paracrine manner, leading to cancer cell metastatic progression. We previously reported a novel S100A8/A9 receptor, neuroplastin-β (NPTNβ), which plays a critical role in atopic dermatitis when it is highly activated in keratinocytes by an excess amount of extracellular S100A8/A9 in the inflammatory skin lesion. Interestingly, our expression profiling of NPTNβ showed significantly high expression levels in lung cancer cell lines in a consistent manner. We hence aimed to determine the significance of NPTNβ as an S100A8/A9 receptor in lung cancer. Our results showed that NPTNβ has strong ability to induce cancer-related cellular events, including anchorage-independent growth, motility and invasiveness, in lung cancer cells in response to extracellular S100A8/A9, eventually leading to the expression of a cancer disseminative phenotype in lung tissue in vivo. Mechanistic investigation revealed that binding of S100A8/A9 to NPTNβ mediates activation of NFIA and NFIB and following SPDEF transcription factors through orchestrated upstream signals from TRAF2 and RAS, which is linked to anchorage-independent growth, motility and invasiveness. Overall, our results indicate the importance of the S100A8/A9-NPTNβ axis in lung cancer disseminative progression and reveal a pivotal role of its newly identified downstream signaling, TRAF2/RAS-NFIA/NFIB-SPDEF, in linking to the aggressive development of lung cancers.

Evaluation of Peripheral Blood Eosinophilia in Adolescent and Adult Patients Suffering from Atopic Dermatitis and the Relation to the Occurrence of Allergy to Aeroallergens.

Background:Eosinophils play an important pathogenic role in atopic dermatitis (AD), but its exact function remains to be determined.Aims and Objectives:The aim of this study was to correlate the eosinophil count with the manifestations such as asthma bronchiale, rhinitis, level of total IgE, sensitization to mites, animal dander, bird feather, dust, mixture of grass, mixture of trees, mixture of fungi, duration of lesions (persistent or occasional during last year), family history about atopy, and onset of AD (under or above 5 year of age).Materials and Methods:Two hundred and seventy-two patients suffering from AD at the age of 14 year or older were examined – 100 men and 172 women with the average age of 26.7±9.5 years and with the average SCORAD index of 32.9±14.1. Complete dermatological and allergological examinations were performed in all patients with the evaluation of monitored manifestations. Mann–Whitney test for difference in medians was used for statistical evaluation.Results:The count of eosinophils in peripheral blood was significantly higher in patients with total IgE ≥200 IU/ml, with sensitization to dust, with persistent eczematous lesions and in patients with the onset of AD under 5 year of age. The count of eosinophils above 5% was recorded as well in patients suffering from asthma bronchiale, rhinitis, sensitization to mites, and in patients with positive family history about atopy, but the difference was not significant. On the other hand, the count of eosinophils was under 5% in patients with sensitization to animal dander, bird feather, mixture of grass and trees.Conclusion:Our results demonstrated the difference in the count of eosinophils in peripheral blood according to different manifestations in patients suffering from AD.

Expression of T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain on CD4+ T cells in patients with atopic dermatitis.

The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4+ T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4+ T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT+ cells among CD4+ T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT+ cells among CD4+ T cells was negatively correlated with both serum thymus and activation-regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4+ T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4+ T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway-based therapeutic approach for AD.

Adhesion of Staphylococcus aureus to Corneocytes from Atopic Dermatitis Patients Is Controlled by Natural Moisturizing Factor Levels.

ABSTRACTThe bacterial pathogen Staphylococcus aureus plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by S. aureus exacerbates the disease, but the molecular determinants of the bacterium-skin adhesive interactions are poorly understood. Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum corneum have been shown to be associated with more severe AD symptoms, but whether this is directly related to S. aureus adhesion is still an open question. Here, we demonstrate a novel relationship between NMF expression in AD skin and strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are covered by a dense layer of nanoscale villus protrusions. S. aureus bacteria isolated from AD skin bind much more strongly to corneocytes when the NMF level is reduced. Strong binding forces originate from a specific interaction between the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably, mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed with catch bonds, demonstrating that physical stress plays a role in promoting colonization of AD skin by S. aureus. Collectively, our findings demonstrate that patient NMF levels regulate the strength of S. aureus-corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments.

Treatment of atopic dermatitis with tralokinumab, an anti–IL-13 mAb

IL-13 has an important role in atopic dermatitis (AD) pathogenesis. Tralokinumab is a fully human mAb that potently and specifically neutralizes IL-13. We sought to evaluate the efficacy and safety of tralokinumab in adults with moderate-to-severe AD. In this phase 2b study (NCT02347176), 204 adults were randomized 1:1:1:1 to receive 45, 150, or 300mg of subcutaneous tralokinumab, or placebo, every 2weeks for 12weeks with concomitant topical glucocorticoids. Coprimary end points were change from baseline in Eczema Area Severity Index score and percentage of participants with an Investigator's Global Assessment response (0/1 score and reduction of ≥2 grades from baseline) at week 12. At week 12, 300mg of tralokinumab significantly improved change from baseline in Eczema Area Severity Index score versus placebo (adjusted mean difference, -4.94; 95% CI, -8.76 to -1.13; P=.01), and a greater percentage of participants achieved an Investigator's Global Assessment response (26.7% vs 11.8%). Greater responses were found in participants with greater concentrations of biomarkers of increased IL-13 activity. Participants treated with 300mg of tralokinumab demonstrated improvements in SCORAD, Dermatology Life Quality Index, and pruritus numeric rating scale (7-day mean) scores versus placebo. Upper respiratory tract infection was the most frequent treatment-emergent adverse event reported as related to study drug in the placebo (3.9%) and pooled tralokinumab (3.9%) groups. Tralokinumab treatment was associated with early and sustained improvements in AD symptoms and an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with AD.

The prevalence of antibody responses against Staphylococcus aureus antigens in patients with atopic dermatitis: a systematic review and meta-analysis

Atopic dermatitis (AD) is a common type of eczema. The bacterium Staphylococcus (S.) aureus plays a role in AD, possibly via various substances that are part of the bacterium. In people with AD, how the body's immune system reacts to these substances might lead to the inflammation seen in AD. In this study, we provide an overview of what is known from current literature (e.g. studies published in medical journals) on the immune response (antibodies) against S. aureus substances (antigens) in AD patients compared to healthy controls (people without AD). Scientific literature was systematically obtained from different databases. We extracted data on how often (so‐called ‘prevalence’) antibodies of, among others, the IgE type directed against S. aureus can be found in AD patients. A weighted prevalence was calculated, as studies with more patients were regarded more relevant, and prevalence was compared between AD patients and healthy controls. Tests for differences between studies and overall study quality were done to interpret the robustness of the results. We included 26 publications with a total of 2369 patients. In 10 studies a control group (of people without AD) was also studied. Study quality was fair to poor. The weighted prevalence of IgE against S. aureus antigens was 33% for staphylococcal enterotoxin (SE) A, 35% for SEB and 16% for toxic shock syndrome toxin (TSST)‐1. Compared to healthy controls, AD patients had 8.37 times more IgE against SEA and 9.37 times more IgE against SEB. No significant difference was seen for IgE against TSST‐1. Interpretation of the results should take into account that there were some important differences in study design and the fact that the studies were generally small. In conclusion, AD patients more often show an IgE antibody response against the S. aureus antigens SEA and SEB compared to healthy controls. These findings show that S. aureus may have a role in AD.

Association between Resistin Gene Polymorphisms and Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disorder. It is characterized by an inappropriate skin barrier function, allergen sensitization, and recurrent skin infections. Resistin is an adipokine expressed mainly in macrophages and monocytes; it has a role in the inflammatory process and is associated with multiple inflammatory human diseases; however, only few studies linked resistin to atopic dermatitis. This study tested the association between G>A (rs3745367) and C>T (rs3219177) single nucleotide polymorphisms (SNPs) of the RETN gene with atopic dermatitis. In addition, it explored the relationship between serum resistin protein and atopic dermatitis. To achieve objectives of this study, 162 atopic dermatitis patients and 161 healthy participants were recruited in the study. A significant association was detected between rs3745367 and atopic dermatitis with age and gender specificity (p < 0.05), while no significant association between rs3219177 and atopic dermatitis was found (p > 0.05). For the serum resistin levels, a significant decrease was indicated in atopic dermatitis patients compared to healthy subjects (p < 0.05). In conclusion, rs3745367 may play a gender and age-specific role in atopic dermatitis. In addition, the significant decrease in the resistin protein level confirmed this association.

CCR4 Is Critically Involved in Skin Allergic Inflammation of BALB/c Mice

Atopic dermatitis is a chronic inflammatory skin disease involving T-helper (Th) 2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in atopic dermatitis remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute atopic dermatitis-like skin lesions in BALB/c mice, a strain prone to Th2 responses, which were characterized by increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions; elevated levels of total and ovalbumin-specific IgE in the sera; and increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions. Of note, the same model was less efficient in C57BL/6 mice, a strain prone to Th1 responses. Using this atopic dermatitis model in BALB/c mice, we demonstrated that CCR4-deficiency or a CCR4 antagonist ameliorated the allergic responses. Collectively, these results demonstrate that CCR4 plays a pivotal role in skin allergic inflammation of BALB/c mice by recruiting CCR4-expressing Th2 cells and Th17 cells.

Prevalence of Atopic Dermatitis Criteria among Textile Workers with Occupational Allergic Contact Dermatitis and Effects of Having Atopic Dermatitis on Contact Antigenic Diversity.

Objectives:Contact dermatitis (CD) is a common skin disease. Occupational contact dermatitis (OCD) is the most frequently seen occupational skin disease and includes both occupational allergic CD (OACD) and occupational irritant CD (OICD). One of the most common sources of OACD is textile products. Individuals with atopic dermatitis (AD) have an increased risk for development of allergic contact dermatitis (ACD). However, the role of AD in the etiopathogenesis of the development of OACD among textile industry workers is not well known. The aim of the present study was to determine the prevalence of AD among textile workers with OACD and to analyze contact antigenic diversity between the workers with and without AD.Methods:A prospective, cross-sectional study was conducted with 352 textile workers who had previously been diagnosed with OACD. The patients were questioned and examined with respect to AD criteria, demographic features, disease duration, duration of employment until first symptoms, phototype, workplace (subsectors), and location of lesions at control visits. Immediate skin test reactivity was evaluated with a commercial skin prick test panel. The data obtained and the patients’ previously recorded patch test results were compared in OACD groups with and without a diagnosis of AD. The results were statistically evaluated with a significance level of p value <0.05.Results:The study population consisted of 124 males and 227 females. The mean age was 35.69±13.65 years. The most commonly seen employment duration, phototype, subsector, and location were 4 to 8 months (26.14%), 9 to 12 months (34.66%), Fitzpatrick type-III (37.50%), dyeing (33.52%), and exclusively the hands (60.51%), respectively. In all, 193 patients (54.83%) met the criteria for the diagnosis of AD. In the OACD group with AD, there was a significant number with 4 major and 16 minor criteria, as well as positivity for 14 contact allergens.Conclusion:Most AD criteria, or a diagnosis of AD, are highly detectable among workers with textile-related OACD. The results for patch test allergens may be significantly higher than those of individuals without AD. Textile workers with AD should be warned about the possibility of the early development of OACD.

Investigation of Immune-Regulatory Effects of Mageumsan Hot Spring via Protein Microarray In Vitro.

BackgroundEmpirical evidences for efficacy of hot spring (HS) water in inflammatory skin disorders have not been substantiated with sufficient, immunological “hard evidence”. Mageumsan HS water, characterized by its weakly-alkaline properties and low total dissolved solids content, has been known to alleviate various immune-inflammatory skin diseases, including atopic dermatitis (AD).ObjectiveThe trial attempted to quantitatively analyze in vitro expression levels of chemical mediators in cutaneous inflammation from HaCaT cell line treated with Mageumsan HS, and suggest the likely mode of action through which it exerts the apparent anti-inflammatory effects in AD.MethodsUsing membrane-based human antibody array kit, customized to include 30 different, keratinocyte-derived mediator proteins, their expression levels (including interleukin [IL]-1, IL-6, IL-8, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, and granulocyte macrophage colony-stimulating factor) were assessed in vitro. Selected key proteins were further quantified with enzyme-linked immunosorbent assay.ResultsThere was a clear pattern of overall suppression of the mediators, especially those noted for their pro-inflammatory role in AD (monocyte chemoattractant protein [MCP]-1, regulated on activation, normal T cell expressed and secreted, cutaneous T-cell-attracting chemokine, Eotaxin, and macrophage inflammatory protein-1α, etc.). Also, reduced expression of involucrin and cytokeratin 1 was also reduced in the HS-treated group.ConclusionThe present study has shown that Mageumsan HS water may exert its effects on inflammatory skin disorders through regulation of proinflammatory cytokines. These evidences are to be supported with further future investigations to elucidate immunological mechanism behind these beneficial effects of HS water in the chronically inflamed skin of AD.

Nasal Colonization by Staphylococcus aureus in Children with Atopic Dermatitis

Background: The cutaneous and nasal microbiota, especially Staphylococcus aureus (S. aureus), plays a key role in atopic dermatitis (AD). Although this association is well known, it is difficult to establish whether colonization by these bacteria is a cause or a consequence of the disease. Objectives: The primary objectives of our study are to determine the prevalence of nasal colonization by S. aureus and its relationship with disease severity in children with AD, as well as to describe the magnitude of the association between the two. Methods: This was an analytical case-control study in children with and without AD. Participants were recruited consecutively upon presenting to the Department of Pediatric Dermatology at the General University Hospital until reaching the estimated sample size of 157 cases and 314 controls (N=471; ratio 1:2). Results: The prevalence of S. aureus nasal colonization was significantly higher in children with AD than in those without (32.5% vs. 23.9%; odds ratio (OR) 1.5, 95% CI 1.0, 2.3; p=0.047). Prevalence of colonization was not higher in the children with severe AD than in those with less severe AD. In multivariable analysis, an independent association (borderline significant) between nasal colonization by S. aureus and AD persisted after adjusting for all other study variables (OR 1.5; 95% CI 0.9, 2.6; p=0.11). Conclusions: Our paper provides further evidence of an association between atopy and nasal colonization by S. aureus, though not between nasal colonization and AD severity. The role of nasal S. aureus and the microbiota in people with AD is a controversial but crucial area of study. Greater knowledge of this topic could be clinically applicable in AD patients.

Expression of Skin Barrier Protein Filaggrin in Skin Diseases without Atopic Dermatitis

The epidermis represents an essential barrier versus a broad range of exogenous stimuli. To form a functional epidermis, keratinocytes express filaggrin which plays a vital role in atopic dermatitis. However the relationship between filaggrin and other skin diseases remains unknown. In our study we chose 5 different common skin diseases and analyzed the expression of filaggrin in the skin using immunohistochemistry. Imiquimod (IMQ)-induced mouse model was used for detecting the filaggrin level and barrier function. The results indicated that the expression of filaggrin is reduced in psoriasis compared to the other skin diseases. Furthermore in vivo study showed that the skin barrier is defected with a decreased expression of filaggrin in IMQ-induced psoriasis mouse model, which is accompanied with an increased level of IL-17/IL-23. In conclusion, the defective skin barrier is involved in the development of psoriasis in human and mice with a reduced expression of filaggrin which may be regulated by the increased level of IL-17/IL-23 in the skin.

Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs.

IL-31 is a cytokine that is believed to play an important role in atopic dermatitis (AD). IL-31 levels positively correlate with disease severity in children with AD. Currently, there is no study that has investigated such a correlation in atopic dogs. The purpose of this study was to evaluate the correlation between IL-31 serum levels and severity of dermatitis. It was hypothesized that a positive correlation exists between severity of AD and circulating levels of IL-31. Sixteen atopic beagles experimentally sensitized to house dust mites. Atopic beagles were exposed to dust mites epicutaneously twice weekly for four weeks. Severity of dermatitis was scored by the Canine Atopic Dermatitis and Extent Severity Index, 3rd iteration (CADESI-03) on days 0 and 28. Blood samples were taken on days 0 and 28 to measure serum IL-31 using a commercially available ELISA. Correlation between CADESI-03 scores and serum IL-31 levels was not detected on day 0 (Pearson, r = -0.2609, P = 0.3291). After flare-up of dermatitis was induced with allergen exposure, a significant positive correlation was detected between serum IL-31 and CADESI-03 on Day 28 (r = 0.6738, P = 0.004). Positive correlation was detected in active disease between severity of dermatitis and circulating levels of IL-31. Additional studies are needed to investigate this correlation in other breeds of dogs and to test whether circulating levels of IL-31 may predict clinical response to biological agents aimed at IL-31.