Maintenance of an Acidic Stratum Corneum Prevents Emergence of Murine Atopic Dermatitis (original) (raw)
2009, Journal of Investigative Dermatology
Neutralization of stratum corneum (SC) adversely impacts key epidermal functions, including permeability barrier homeostasis and SC integrity. Conversely, acidification of SC improves these functions in developmentally impaired (neonatal or aged) skin, and enhances function in normal skin. Hence, we hypothesized that acidification could alter the course of inflammatory dermatoses, which invariably exhibit an increased SC pH. Maintenance of a low pH by topical applications of the polyhydroxyl acid, lactobionic acid, during the repeated-challenge phase inhibited the development of oxazolone-induced atopic dermatitis (AD). Neither gross/histological dermatitis nor altered barrier function developed, and emergence of epidermal hyperplasia was prevented; however, cytokine generation decreased. Acidification also largely normalized the development of hapten-induced changes in eosinophil/mast cell densities, density of chemoattractant receptor-homologous molecule expressed on TH2-positive lymphocytes, and serum IgE levels. The pH-induced improvement in barrier function most likely accounts for the anti-inflammatory activity, which could be further attributed to normalization of both lamellar body secretion and lamellar bilayer formation. Acidification of SC alone substantially prevents development of barrier abnormalities and downstream immune abnormalities during the elicitation phase of murine AD. These results provide direct evidence for the "outside-inside" pathogenesis of AD and further suggest that maintenance of an acidic SC pH could prevent the emergence of AD in humans.
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Journal of Investigative Dermatology, 2008
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.
THE SKIN BARRIER FUNCTION AND THE DEVELOPMENT OF DERMATITIS.
The skin barrier is a very important element of the body as it plays crucial roles in the immune surveillance and epidermal homeostasis, and in stopping entrance of microorganisms and allergens. The capacity of the skin to protect the body relies on its structure that includes different layers of cells containing components such proteins and lipids organized in such a way that they provide a tight and strong structure to the skin. Due to various factors, impairments of the structural integrity of the skin occur and compromise its barrier functions provoking thereby immune responses that lead to inflammatory reactions responsible for skin diseases such as dermatitis. According to the causative agent, the location and the symptoms, different types of dermatitis can be identified. These include for example allergic contact dermatitis, atopic dermatitis known as eczema, seborrheic dermatitis and nummular dermatitis. Common symptoms are associated with dry and itchy skin accompanied by the occurrence of blisters. Both genetics and environmental factors play a role in the occurrence of dermatitis. The genetic factors include mutations in genes coding for important skin proteins such as filaggrin responsible for different functions mainly in relation to water retention. Environmental factors can be associated with allergens, detergent, surfactant, excessive washing and exfoliation, and inappropriate diet. This research paper provides an overview of the occurrence of dermatitis in relation to defects in the skin barrier function. Different types of dermatitis, the normal skin structure components, and its associated functions are discussed. Moreover, the basis for structural defects in the skin in relation to mainly atopic dermatitis, with an emphasis on filaggrin and its genetic underpinnings are reviewed. Aspects of the innate and adaptive immunity, including the role of anti-microbial peptides and proteases are also depicted.
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