Short-term glucocorticoid treatment compromises both permeability barrier homeostasis and stratum corneum integrity: inhibition of epidermal lipid synthesis accounts for functional abnormalities
| Autor: | Jean-Pierre Hachem, Kenneth R. Feingold, Joachim W. Fluhr, Debra Crumrine, Ashley J. Fowler, Sung Ku Ahn, Barbara E. Brown, Peter M. Elias, Mao-Qiang Man, Jack Kao |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Administration Topical Anti-Inflammatory Agents Lamellar granule Biochemistry stratum corneum integrity 030207 dermatology & venereal diseases Mice 0302 clinical medicine Homeostasis Barrier function 0303 health sciences integumentary system Desmosomes Middle Aged Lipids 3. Good health medicine.anatomical_structure Glucocorticoid medicine.drug Adult medicine.medical_specialty Dermatology Biology Drug Administration Schedule Permeability 03 medical and health sciences Internal medicine medicine Stratum corneum lipid synthesis Animals Humans permeability barrier function lamellar bodies Molecular Biology Glucocorticoids 030304 developmental biology Transepidermal water loss Clobetasol Mice Hairless Epidermis (botany) corneodesmosomes transepidermal water loss Lipid metabolism Cell Biology Microscopy Electron Endocrinology Epidermis |
| Zdroj: | The Journal of investigative dermatology. 120(3) |
| ISSN: | 0022-202X |
| Popis: | Prolonged exposure of human epidermis to excess endogenous or exogenous glucocorticoids can result in well-recognized cutaneous abnormalities. Here, we determined whether short-term glucocorticoid treatment would also display adverse effects, specifically on two key epidermal functions, permeability barrier homeostasis and stratum corneum integrity and cohesion, and the basis for such changes. In humans 3 d of treatment with a potent, commonly employed topical glucocorticoid (clobetasol), applied topically, produced a deterioration in barrier homeostasis, characterized by delayed barrier recovery and abnormal stratum corneum integrity (rate of barrier disruption with tape strippings) and stratum corneum cohesion (microg protein removed per stripping). Short-term systemic and topical glucocorticoid produced similar functional defects in mice, where the basis for these abnormalities was explored further. Both the production and secretion of lamellar bodies were profoundly decreased in topical glucocorticoid-treated mice resulting in decreased extracellular lamellar bilayers. These structural changes, in turn, were attributable to a profound global inhibition of lipid synthesis, demonstrated both in epidermis and in cultured human keratinocytes. The basis for the abnormality in stratum corneum integrity and cohesion was a diminution in the density of corneodesmosomes in the lower stratum corneum. We next performed topical replacement studies to determine whether lipid deficiency accounts for the glucocorticoid-induced functional abnormalities. The abnormalities in both permeability barrier homeostasis and stratum corneum integrity were corrected by topical applications of an equimolar distribution of free fatty acids, cholesterol, and ceramides, indicating that glucocorticoid-induced inhibition of epidermal lipid synthesis accounts for the derangements in both cutaneous barrier function and stratum corneum integrity/cohesion. These studies indicate that even short-term exposure to potent glucocorticosteroids can exert profound negative effects on cutaneous structure and function. Finally, topical replenishment with epidermal physiologic lipids could represent a potential method to reduce the adverse cutaneous effects of both topical glucocorticoid treatment and Cushing's syndrome. |
| Databáze: | OpenAIRE |
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