| Evaluation of Anti-inflammatory and Atrophogenic Effects of Glucocorticoids on Reconstructed Human Skin. | |
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MedLine Citation:
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PMID: 21639680 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Topical glucocorticoids (GCs) are extensively used in the treatment of inflammatory skin diseases. However, their long-term use is often accompanied by severe and eventually irreversible adverse effects, with atrophy being the most important limitation. Currently, most non-clinical studies involve animal testing, so the results are not always representative of the situation in humans. The aim of this project was to establish an in vitro test protocol for the evaluation of the anti-inflammatory and atrophic potential of topically applied GCs in reconstructed human skin. Initial studies with fibroblasts and keratinocytes confirmed the anti-inflammatory and atrophogenic effects of GCs, as evidenced by decreased cytokine production and collagen mRNA expression. In non-pretreated reconstructed human skin (EpiDermFT(TM)), the topical application of GCs for seven days strongly reduced the secretion of interleukin (IL)-6. GC-induced skin atrophy, known to appear only after prolonged treatment, was not detected by the analysis of epidermal thickness and collagen mRNA expression. However, reproducible epidermal inflammation was established for the first time in reconstructed human skin. Topical treatment with tumour necrosis factor (TNF) increased IL-6 release and strongly reduced epidermal thickness accompanied by severe parakeratosis. GC treatment of reconstructed human skin reduced IL-6 levels and completely resolved parakeratosis, leading to the normalisation of epidermal thickness. These induced inflammatory conditions mimic more closely the clinical situations in which GCs are used, and therefore appear to be more suitable for future investigations for the establishment of a human-based in vitro test protocol for evaluating wanted and unwanted GC effects. |
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Authors:
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Günther Weindl; Francesca Castello; Monika Schäfer-Korting |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Alternatives to laboratory animals : ATLA Volume: 39 ISSN: 0261-1929 ISO Abbreviation: Altern Lab Anim Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-06-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8110074 Medline TA: Altern Lab Anim Country: England |
Other Details:
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Languages: eng Pagination: 173-87 Citation Subset: IM |
Copyright Information:
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2011 FRAME. |
Affiliation:
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Institut für Pharmazie (Pharmakologie und Toxikologie), Freie Universität Berlin, Berlin, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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