Dataset Information

Trichohyalin gene expression is negatively correlated with the severity of dermatitis in a canine atopic dermatitis model.

ABSTRACT:

Introduction

Canine atopic dermatitis (AD) closely mimics human AD and is recognized as a beneficial animal model. House dust mites (HDM) are a common allergen for both species. The effects of chronic exposure to HDM on the skin have not been studied in this animal model, and it is not known how changes in gene expression correlate to the severity of dermatitis.

Methods

We used an established canine model of AD and took biopsies before HDM exposure (D0) and five times during repeated allergen challenges (on Days 1, 2, 8, 15, and 29, hereafter referred to as D1, D2, D8, D15, and D29). The severity of dermatitis was scored on the same days.

Results

Trichohyalin (TCHH) gene expression decreased the most (15-fold decrease on D29 vs. D0) and negatively correlated with the severity of dermatitis. Gap-junction protein gene expression increased over 3-fold on D1, D8, and D29 and positively correlated with the severity of dermatitis. Compared to D0, IL-31 gene expression significantly increased on D8 (p = 0.0098), D15 (p = 0.0068), and D29 (p = 0.0187), but the correlation with the severity of dermatitis did not reach significance.

Discussion

This is the first report on trichohyalin, a protein belonging to the S100 family, and gap-junction protein gene expression in the context of the clinical severity of AD. We propose that these proteins should be further investigated to better understand their role in this complex disease.

SUBMITTER: Marsella R

PROVIDER: S-EPMC11371671 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Trichohyalin gene expression is negatively correlated with the severity of dermatitis in a canine atopic dermatitis model.

Marsella Rosanna R Ahrens Kim K Wilkes Rachel R Munguia Nathalie N

Frontiers in veterinary science 20240821

<h4>Introduction</h4>Canine atopic dermatitis (AD) closely mimics human AD and is recognized as a beneficial animal model. House dust mites (HDM) are a common allergen for both species. The effects of chronic exposure to HDM on the skin have not been studied in this animal model, and it is not known how changes in gene expression correlate to the severity of dermatitis.<h4>Methods</h4>We used an established canine model of AD and took biopsies before HDM exposure (D0) and five times during repea ...[more]

PMID: 39234173

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Project description:BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.ObjectiveThis study aimed to identify historical and clinical features and biomarkers associated with AD severity.MethodsA US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity.ResultsParticipants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001).ConclusionsIn a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.

Project description:BACKGROUND:Skin barrier dysfunction plays a key role in atopic dermatitis (AD). This impairment is related to altered composition and metabolism of epidermal sphingolipids and a deficiency of ceramides. Glycosaminoglycans (GAGs), and especially hyaluronic acid, could be useful in the management of AD. This study aimed to evaluate the effects of a novel topical treatment consisting of sphingolipids and GAGs extracts in dogs with AD. This formulation is different from previously tested products because the sphingolipid extract contained high amounts of sphingomyelin, a precursor of ceramides, and this has been shown to enhance endogenous synthesis of ceramides and to increase lamellar-related structures in vitro. Thus, it was hypothesized that this formulation could improve clinical disease and skin barrier function in patients with AD. RESULTS:Twelve house dust mite (HDM) allergic atopic beagle dogs were randomized into two groups: control (n = 6; no treatment) or treatment (n = 6; topical sphingolipids and GAGs twice weekly for 8 weeks). Dogs were challenged with allergen twice weekly and the severity of dermatitis was scored using the canine atopic dermatitis and extent severity index (CADESI-03) once weekly. Skin barrier function (measurement of transepidermal water loss) and severity of pruritus (both pruritus visual analog scale [PVAS] and pruritus timed episodes) were assessed at 0, 4 and 8 weeks of treatment. Assessments were done by personnel unaware of group allocation. Complete blood count, serum biochemistry and stratum corneum (SC) lipidomics analyses were done at baseline and at week 8. Compared to baseline, significant increases in CADESI (P = 0.0003) and PVAS (P = 0.041) were observed only in the control group, and SC polyunsaturated fatty acids increased significantly only with treatment (P = 0.039). Compared to control, treatment group had a significantly lower CADESI after 1 week (P = 0.0078) and a significantly lower PVAS after 8 weeks (P = 0.0448). Treatment was well tolerated. CONCLUSIONS:In this study in dogs with AD, a new topical formulation containing sphingomyelin-rich sphingolipids plus GAGs extracts attenuated the clinical worsening induced by HDM, supporting its use in atopic patients, either as an adjunctive treatment or used as monotherapy in certain cases.

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Project description:There is no established protocol for the development of an experimental canine atopic dermatitis model in laboratory beagles. This study aimed to establish an experimental model that mimics spontaneous canine atopic dermatitis (CAD) clinically, immunologically, and microbiologically, by repeated epicutaneous applications of mite antigens and to describe the entire process including sensitization and provocation in detail for reproducibility. Six intact male laboratory beagle dogs aged 14 months were included in this study. During the sensitization and provocation phase, the house dust mite (HDM) paste consisted of Dermatophagoides farinae (Der f ) and mineral oil, which was applied focally to the 10 × 10 cm area of the right groin as evenly as possible. Further, 120 mg of Der f was applied to each dog twice a week for 12 weeks during the sensitization phase and 25 mg and 120 mg was applied to each dog for the first 2 weeks and subsequent 2 weeks, respectively, during the provocation phase. Thereafter, the applied area was covered with a dressing. Skin lesions including erythema, hyperpigmentation, excoriation, and lichenification were induced and exacerbated gradually through the experimental time course in all six dogs. The canine atopic dermatitis extent and severity index (CADESI) score and transepidermal water loss (TEWL) significantly increased after sensitization and provocation. IL-13 and IL-31 levels increased significantly after provocation as a result of the activation of the T helper-2 (Th2) response. On the contrary, the IL-10 levels decreased significantly after sensitization, which suggested a suppression of Tregs activity. After the completion of provocation, skin microbiome analysis showed that Firmicutes was the most abundant phylum, which indicated bacterial dysbiosis. This study demonstrated that epicutaneous application of HDM in beagle dogs resulted in the elevation of serum HDM-specific IgE levels and clinical atopic scores, a high TEWL, and microbiome dysbiosis resembling spontaneous CAD. These results suggest that this tailored protocol of epicutaneous exposure to Der f may provide support for the development of the experimental CAD model in laboratory beagles.

Dataset Information

Trichohyalin gene expression is negatively correlated with the severity of dermatitis in a canine atopic dermatitis model.

Introduction

Methods

Results

Discussion

Publications

Trichohyalin gene expression is negatively correlated with the severity of dermatitis in a canine atopic dermatitis model.

Similar Datasets

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