Dermal Exposure to the Immunomodulatory Antimicrobial Chemical Triclosan Alters the Skin Barrier Integrity and Microbiome in Mice

Abstract Triclosan is an antimicrobial chemical used in healthcare settings that can be absorbed through the skin. Exposure to triclosan has been positively associated with food and aeroallergy and asthma exacerbation in humans and, although not directly sensitizing, has been demonstrated to augment the allergic response in a mouse model of asthma. The skin barrier and microbiome are thought to play important roles in regulating inflammation and allergy and disruptions may contribute to development of allergic disease. To investigate potential connections of the skin barrier and microbiome with immune responses to triclosan, SKH1 mice were exposed dermally to triclosan (0.5–2%) or vehicle for up to 7 consecutive days. Exposure to 2% triclosan for 5–7 days on the skin was shown to increase transepidermal water loss levels. Seven days of dermal exposure to triclosan decreased filaggrin 2 and keratin 10 expression, but increased filaggrin and keratin 14 protein along with the danger signal S100a8 and interleukin-4. Dermal exposure to triclosan for 7 days also altered the alpha and beta diversity of the skin and gut microbiome. Specifically, dermal triclosan exposure increased the relative abundance of the Firmicutes family, Lachnospiraceae on the skin but decreased the abundance of Firmicutes family, Ruminococcaceae in the gut. Collectively, these results demonstrate that repeated dermal exposure to the antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice, suggesting that these changes may contribute to the increase in allergic immune responses following dermal exposure to triclosan.

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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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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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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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Skin Barrier Integrity and Natural Moisturising Factor Levels After Cumulative Dermal Exposure to Alkaline Agents in Atopic Dermatitis

Acta Dermato Venereologica ◽

10.2340/00015555-1815 ◽

2014 ◽

Vol 94 (6) ◽

pp. 640-644 ◽

Cited By ~ 39

Author(s):

I Angelova-Fischer ◽

I Dapic ◽

A Hoek ◽

I Jakasa ◽

T Fischer ◽

...

Keyword(s):

Atopic Dermatitis ◽

Skin Barrier ◽

Dermal Exposure ◽

Barrier Integrity

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Wikstroemia ganpi Extract Improved Atopic Dermatitis-Like Skin Lesions via Suppression of Interleukin-4 in 2,4-Dinitrochlorobenzene-Induced SKH-1 Hairless Mice

Molecules ◽

10.3390/molecules26072016 ◽

2021 ◽

Vol 26 (7) ◽

pp. 2016

Author(s):

Jonghwan Jegal ◽

No-June Park ◽

Beom-Geun Jo ◽

Tae-Young Kim ◽

Sim-Kyu Bong ◽

...

Keyword(s):

Atopic Dermatitis ◽

Inflammatory Diseases ◽

Skin Barrier ◽

Ethanolic Extract ◽

Inflammatory Cells ◽

Skin Lesions ◽

Transepidermal Water Loss ◽

Interleukin 4 ◽

Skin Barrier Function ◽

Blood Levels

Plants of the genus Wikstroemia are used in Chinese traditional medicine to treat inflammatory diseases, such as arthritis, bronchitis, and pneumonia. The present study was designed to determine whether Wikstroemia ganpi (Siebold and Zucc.) Maxim. offers a potential means of treating 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Symptoms such as redness, edema, and keratinization in AD mice induced by DNCB were alleviated by the co-application of an ethanolic extract of W. ganpi for 2 weeks. The severity of skin barrier function damage was evaluated by measuring TEWL (transepidermal water loss). TEWLs of DNCB sensitized mouse dorsal skin were reduced by the application of a W. ganpi ethanolic extract, and skin hydration was increased. In addition, the infiltration of inflammatory cells into the dermis was significantly reduced, as were blood levels of IgE and IL-4, which play an important role in the expression of AD. The results of this experiment suggest that W. ganpi is a potential therapeutic agent for AD.

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NATURAL COSMETICS IN THE CARE OF YOUNG CHILDREN

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2020-99-6-155-162 ◽

2020 ◽

Vol 99 (6) ◽

pp. 155-162

Author(s):

O.B. Tamrazova ◽

◽

S.P. Seleznev ◽

A.V. Tamrazova ◽

◽

...

Keyword(s):

Skin Barrier ◽

Structural Features ◽

Transepidermal Water Loss ◽

General Information ◽

Skin Barrier Function ◽

Skin Physiology ◽

Main Emphasis ◽

Antimicrobial Protection ◽

Irritant Dermatitis ◽

Adaptive Shifts

The article provides general information about the skin physiology of newborns and infants. Structural features of the skin and main adaptive shifts in newborns, are described. Тhe child has an increase in the skin barrier function of the skin, which prevents transepidermal water loss; active synthesis of natural moisturizing factor (NMF) components that control skin hydration; shift of pH to acidic environment; normalization of thermoregulatory functions; enhancement of the photoprotective function; immune restructuring for antimicrobial protection; formation of a normal microbiome. The article describes the consequences of improper skin care of a newborn, using the example of diaper dermatitis, irritant dermatitis, prickly heat and vesiculopustulosis. The importance of using specialized children's cosmetics in caring for an infant is assessed. The basic recommendations for the choice of these products are presented, where the main emphasis is on the choice of products consisting of natural ingredients. Giving preference to natural cosmetics, everyone should carefully study the composition of these products and trust the manufacturers who can guarantee safety of care products for the youngest children.

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Type 2 immunity induced by bladder extracellular matrix enhances corneal wound healing

Science Advances ◽

10.1126/sciadv.abe2635 ◽

2021 ◽

Vol 7 (16) ◽

pp. eabe2635

Author(s):

Xiaokun Wang ◽

Liam Chung ◽

Joshua Hooks ◽

David R. Maestas ◽

Andriana Lebid ◽

...

Keyword(s):

Wound Healing ◽

Immune Responses ◽

Smooth Muscle Actin ◽

Treated Group ◽

Interleukin 4 ◽

Impaired Wound Healing ◽

Urinary Bladder Matrix ◽

Incomplete Healing ◽

Haze Formation

The avascular nature of cornea tissue limits its regenerative potential, which may lead to incomplete healing and formation of scars when damaged. Here, we applied micro- and ultrafine porcine urinary bladder matrix (UBM) particulate to promote type 2 immune responses in cornea wounds. Results demonstrated that UBM particulate substantially reduced corneal haze formation as compared to the saline-treated group. Flow cytometry and gene expression analysis showed that UBM particulate suppressed the differentiation of corneal stromal cells into α-smooth muscle actin–positive (αSMA+) myofibroblasts. UBM treatments up-regulated interleukin-4 (IL-4) produced primarily by eosinophils in the wounded corneas and CD4+ T cells in draining lymph nodes, suggesting a cross-talk between local and peripheral immunity. Gata1−/− mice lacking eosinophils did not respond to UBM treatment and had impaired wound healing. In summary, stimulating type 2 immune responses in the wounded cornea can promote proregenerative environments that lead to improved wound healing for vision restoration.

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A31 COMPLEX ROLE OF DIETARY FIBERS IN IBD: MICROBES MEDIATE FIBER-INDUCED INFLAMMATION

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.030 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 148-150

Author(s):

H Armstrong ◽

R Valcheva ◽

D Santer ◽

Z Zhang ◽

A Rieger ◽

...

Keyword(s):

Immune Responses ◽

Anaerobic Fermentation ◽

Ex Vivo ◽

Severe Disease ◽

Cytokine Secretion ◽

Dietary Fibers ◽

Gut Health ◽

T84 Cells ◽

Microbial Composition ◽

Barrier Integrity

Abstract Background Dietary fibers pass through the bowel undigested and are fermented within the intestine by microbes, typically promoting gut health. However, many IBD patients describe experiencing sensitivity to fibers. β-glucan, found on the surface of fungal cells during fungal infection, has been shown to bind to fiber receptors, such as Dectin-1, on host immune cells, resulting in a pro-inflammatory response. These fungal fibres share properties with dietary fibers. Aims As an altered gut microbial composition has been associated with IBD, we hypothesized that the loss of fiber-fermenting microbes populating the gut in IBD could lead to dietary fibers not being efficiently broken down into their beneficial biproducts (e.g. short chain fatty acids; SCFA), resulting in binding of intact fibers to pro-inflammatory host cell receptors. Methods Immune and epithelial cell lines and colonic biopsies cultured ex vivo were incubated with oligofructose or inulin (5g/L), or pre-fermented fibers (24hr anaerobic fermentation). Immune responses were measured by cytokine secretion (ELISA), and expression (qPCR). Barrier integrity was measured by transepithelial resistance (TEER). Food frequency questionnaire (FFQ) data of patient fiber consumption were correlated with gut microbes (shotgun sequencing) and immune responses to fiber in patient biopsies. Results Unfermented oligofructose induced IL-1β secretion in leukocytes (macrophage, T cell, neutrophil) and in colon biopsies from pediatric Crohn disease (CD; n=38) and ulcerative colitis (UC; n=20) patients cultured ex vivo, but not in non-IBD patients (n=21). IL-1β secretion was greater in patients with more severe disease. Pre-fermentation of oligofructose by whole-microbe intestinal washes from non-IBD patients or remission patients reduced secretion of IL-1β, while whole microbe intestinal washes from severe IBD patients were unable to ferment oligofructose or reduce cytokine secretion. Fiber effects on IL-1β secretion in biopsies positively correlated with effects on barrier integrity in T84 cells. Fiber-associated immune responses in patient biopsies cultured ex vivo (ELISA) correlated with fiber avoidance (FFQ) and gut microbiome (sequencing) in matching patient samples. Conclusions Our findings demonstrate that intolerance and avoidance of prebiotic fibers in select IBD patients is associated with the inability to ferment these fibers, leading to pro-inflammatory immune responses and intestinal barrier disruption. This highlights select disease state scenarios, in which administration of fermentable fibers should be avoided and tailored dietary interventions should be considered in IBD patients. Funding Agencies CIHRWeston Foundation

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The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

International Journal of Molecular Sciences ◽

10.3390/ijms22137227 ◽

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.

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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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