Search

To investigate the effect of emollient on atopic march in a murine model of atopic dermatitis (AD). Following induction of AD with topical calcipotriol (MC903) and ovalbumin (OVA), one group of mice was treated topically with a linoleic acid‐ceramide‐containing emollient, while mice without emollient treatment served as disease controls. After 28 days, clinical, histological and transcriptomic analyses were performed in the skin lesions and the lung as well as serum cytokine levels. Treatments of mice with MC903 and OVA induced a typical phenotype of AD, accompanied by increased expression levels of Th2 and basophil‐related genes in the lung. Topical emollients markedly decreased the severity of skin lesions and inflammatory cell infiltration. Moreover, emollient treatments significantly downregulated expression levels of AD‐related genes (286 of 1450 differentially expressed genes), including those related to innate inflammation (S100a8/a9, Il1b, Defb3/6, Mmp12), chemokines (Cxcl1/3, Ccl3/4) and epidermal permeability barrier (Krt2/6b/80, Serpinb12, Lce3e, Sprr2), etc. Downregulated genes were enriched in mitochondrial OXPHOS‐related pathways, while upregulated genes were mainly enriched in axon guidance and tight junctions. Moreover, topical emollient treatments decreased total serum levels of IL‐4, along with substantial reductions in IgE and thymic stromal lymphopoietin (TSLP) levels. Furthermore, 187 of 275 upregulated genes in lung tissue were also significantly downregulated, including those involved in leucocyte chemotaxis (Ccl9, Ccr2, Retnlg, Ccl3, Cxcl10, Il1r2, etc.) and basophil activation (Mcpt8, Cd200r3, Fcer1a, Ms4a2). In conclusion, topical emollient not only reduces skin inflammation, but also mitigates systemic inflammation by decreasing TSLP and IgE levels. Moreover, topical emollient reduces chemokine production and basophil infiltration and activation in the lung. [ABSTRACT FROM AUTHOR]

The presence of congenitally impaired skin barrier followed by atopic dermatitis ( AD) is an initial step in the atopic march. The maintenance of acidic pH in the stratum corneum ( SC) has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. To determine whether an AD murine model, flaky tail mice, with inherited filaggrin deficiency could develop airway inflammation by repeated topical application followed by nasal inhalation of house dust mite ( HDM) antigen (defined as a novel 'atopic march animal model'), and whether maintenance of an acidic SC environment by continuous application of acidic cream could interrupt the following atopic march. During the course of HDM treatment, acidic cream ( pH2.8) or neutral cream ( pH7.4) was applied to flaky tail mice twice daily. Repeated applications and inhalations of HDM to flaky tail mice induced AD skin lesions followed by respiratory allergies. Maintenance of SC acidity inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. Collectively, a novel atopic march model could be developed by repeated epicutaneous and nasal applications of HDM to flaky tail mice, and that the acidification of SC could prevent the atopic march from AD to respiratory allergy. [ABSTRACT FROM AUTHOR]

Long-standing or repeated skin barrier damage followed by atopic dermatitis (AD) is the initial step of the atopic march that eventually progresses to respiratory allergies. Maintenance of an acidic pH in the stratum corneum (SC) is an important factor for normal skin barrier function. We performed this study to determine whether an oxazolone (Ox)-induced AD murine model can develop airway inflammation by topical application and nasal inhalation of a house dust mite, Dermatofagoides pteronyssinus (Dp), which is a novel 'atopic march animal model', and whether an acidic SC environment, made by repeated application of acidic cream, can interrupt this atopic march. During repeated treatment with Ox and Dp to make an atopic march murine model, acidic cream ( pH 2.8) and neutral cream ( pH 7.4) adjusted by citric acid and sodium hydroxide mixed with vehicle were applied twice daily. Repeated treatment with Ox and Dp to hairless mice induced AD-like skin lesions followed by respiratory allergy, defining it as an atopic march model. Acidic cream inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. These results indicate that a novel atopic march animal model can be developed by repeated topical and nasal treatments with house dust mite on Ox-induced AD mice and that the acidification of SC could be a novel intervention method to block the atopic march. [ABSTRACT FROM AUTHOR]