RESUMEN
BACKGROUND: Atopic dermatitis (AD) in adults and profile of skin barrier proteins and inflammatory cytokines. OBJECTIVE: Evaluation of the expression of skin barrier proteins such as filaggrin, claudins 1 and 4 and of circulating inflammatory cytokines (Th1/Th2/Th17) in adults with AD. METHODS: Thirty-three adult patients with AD diagnosed according to the Hanifin & Rajkacriteria, and 25 healthy controls were enrolled in the study. AD severity was measured by Eczema Area and Severity Index (EASI). Laboratory assays included immunohistochemistry analysis of skin barrier proteins, such as filaggrin, claudins 1 and 4 and interleukin-17 (IL-17) from skin samples and determination of circulating cytokine levels (IL-2, 4, 5, 6, 10, 17A, TNF and IFN-γ) by flow cytometry (Cytometric Bead Array). RESULTS: We observed a reduced expression of filaggrin and claudin 1 in lesional skin of AD patients, when compared to controls. There was an inverse correlation of filaggrin expression and disease severity. In addition, IL-17 expression was enhanced in AD patients. Similarly, higher levels of inflammatory cytokines (IL-2, 5, 6, 10, 17A and IFN-γ) were found in AD patients. CONCLUSION: Our data reinforce the role of an altered skin barrier in the pathogenesis of AD. Our results show not only reduced expression of filaggrin and claudin 1 in lesional atopic skin but also inverse correlation of filaggrin expression and disease severity. Moreover, elevation of in situ IL-17 and of circulating interleukin levels in AD emphasize the systemic, inflammatory profile of this defective skin barrier dermatosis.
Asunto(s)
Dermatitis Atópica/metabolismo , Interleucinas/sangre , Fenómenos Fisiológicos de la Piel , Piel/química , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Claudina-1/análisis , Claudina-1/metabolismo , Claudina-4/análisis , Claudina-4/metabolismo , Femenino , Proteínas Filagrina , Humanos , Interferón gamma/sangre , Interleucina-17/metabolismo , Proteínas de Filamentos Intermediarios/análisis , Proteínas de Filamentos Intermediarios/metabolismo , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
The molecular mechanisms stimulated by vitamin D and low calcium diets that promote intestinal calcium absorption are not fully understood. In the present experiments, groups of chicks were subjected to the following treatments known to alter the efficiency of Ca absorption: vitamin D deficiency, repletion of vitamin D-deficient chicks with 1,25-dihydroxycholecalciferol [1,25(OH)2D3], low Ca intakes, and aluminum toxicity. Duodenal mucosal scrapings were obtained and screened for changes in protein composition using SDS-PAGE and size exclusion chromatography. The relative amount of a previously unreported 400-kDa oligomer containing 22-kDa monomeric subunits was found to vary directly with theoretical changes in the efficiency of Ca absorption, i.e., amounts increased with low Ca intakes and repletion with 1,25(OH)2D3, but were decreased by dietary aluminum and vitamin D deficiency. The oligomer was shown to have Ca-binding activity using a 45Ca overlay technique. These properties suggest 1) that the protein is regulated, at least indirectly, by 1,25(OH)2D3; 2) that the protein may play a role in promoting Ca absorption, possibly by binding Ca; and 3) that dietary aluminum interferes with the regulation of this protein, possibly by interfering with the actions of vitamin D in the intestine.