Characterization of a Hapten-Induced, Murine Model with Multiple Features of Atopic Dermatitis: Structural, Immunologic, and Biochemical Changes following Single Versus Multiple Oxazolone Challenges

Abstract

Atopic dermatitis (AD) is a chronic dermatosis bearing clinical, histological, and immunologic similarities to chronic allergic contact dermatitis (ACD). AD shows a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels, a permeability barrier abnormality, and Staphylococcus aureus colonization. Repeated hapten challenges reportedly produce a Th2-like hypersensitivity reaction (Th2-like HR). Here, 9-10 challenges with oxazolone (Ox) to hairless mice also produced a chronic Th2-like HR. Permeability barrier function and expression of differentiation proteins, filaggrin, loricrin, and involucrin, became abnormal. CRTH-positive Th2-dominant inflammatory infiltrate, with increased IL-4 expression, and a large increase in serum IgE levels were observed. The barrier abnormality was associated with decreased stratum corneum (SC) ceramide content and impaired lamellar body secretion, resulting in abnormal lamellar membranes, as in human AD. Furthermore, as in human AD, epidermal serine protease activity in SC increased and expression of two lamellar body-derived antimicrobial peptides, CRAMP and mBD3, declined after Ox challenges, paralleling the decrease of their human homologues in AD. Thus, multiple Ox challenges to normal murine skin produce a chronic Th2-like HR, with multiple features of human AD. Because of its reproducibility, predictability, and low cost, this model could prove useful for evaluating both pathogenic mechanisms and potential therapies for AD.

Development of Novel Elastic Vesicle-Based Topical Formulation of Cetirizine Dihydrochloride for Treatment of Atopic Dermatitis

“…Animals were divided into four groups (A, B, C, and D) containing four animals per group (Table V). Ten microliter of oxazolone (5% w/v in ethanol) was topically applied daily for a week to animals of group B, C, and D. After 1 week, the oxazolone-treated groups were further treated topically with 60 μL oxazolone (0.1% w/v in ethanol) once every alternate day for an additional 2-week period (19). After half an hour of oxazolone application, cetirizine cream base formulation and cetirizine EV gel each containing 1.0 mg drug was applied daily on the back of animals of groups C and D, respectively.…”

“…AD with signs of acute erythema and pruritus was produced by oxazolone challenge on the back skin of mice (19). While a single oxazolone challenge to hairless mice skin produces an acute AD, 9-10 oxazolone challenges over a 3-week period provoked a persistent chronic dermatosis with evidence of moderate to severe pruritus.…”

Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis

“…Since the seminal work of the McLean Lab has underscored the importance of skin barrier abnormalities as an etiological factor in AD, we focused on the effects of coal tar on the epidermal biology of this disease (1, 3, 8). Our results reveal a key role of the AHR signaling pathway in breaching the vicious The immunopathogenesis of AD has been studied directly on patients or in animal models based on allergic immune responses (29)(30)(31). We have recently developed in vitro organotypic models for psoriasis and AD (18,19), and have shown that the application of genetic techniques in these models could be used to study epidermal aspects of diseases (32).…”

Two Functionally Distinct Subsets of Mast Cells Discriminated By IL-2–Independent CD25 Activities

“…Because CD25pos cells produced higher levels of IL-2 than the CD25neg ones did (Fig. 1F), we set out to investigate the response of these two subsets in vivo in the context of chronic oxazolone-induced contact sensitivity (35). To this purpose, we compared WT cells to CD25KO cells, as well as sorted CD25pos and CD25neg cells.…”