| Type 2 helper T-cell cytokines induce morphologic and molecular characteristics of atopic dermatitis in human skin equivalent. | |
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MedLine Citation:
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PMID: 21514424 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Both the immune system and the epidermis likely have an important role in the pathogenesis of atopic dermatitis (AD). The objective of the present study was to develop a human skin equivalent model exhibiting morphologic and molecular characteristics of AD in a controlled manner. Skin equivalents generated from normal adult human keratinocytes were stimulated with type 2 T-helper cell (Th2) cytokines IL-4 and IL-13, and morphologic features and gene expression of the epidermis were studied. Th2 cytokines induced intercellular edema similar to spongiotic changes observed in lesional AD as assessed at histopathologic analysis and electron microscopy. Furthermore, genes known to be specifically expressed in epidermis of patients with AD such as CAII and NELL2 were induced. In contrast, expression of psoriasis-associated genes such as elafin and hBD2 was not changed. Th2 cytokines caused DNA fragmentation in the keratinocytes, which could be inhibited by the caspase inhibitor Z-VAD, which suggests that apoptosis was induced. In addition, up-regulation of the death receptor Fas was observed in keratinocytes after Th2 cytokine stimulation. IL-4 and IL-13 induced phosphorylation of the signaling molecule STAT6. It was concluded that the skin equivalent model described herein may be useful in investigation of the epidermal aspects of AD and for study of drugs that act at the level of keratinocyte biology. |
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Authors:
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Marijke Kamsteeg; Mieke Bergers; Roelie de Boer; Patrick L J M Zeeuwen; Stanleyson V Hato; Joost Schalkwijk; Geuranne S Tjabringa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of pathology Volume: 178 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-25 Completed Date: 2011-08-26 Revised Date: 2012-05-01 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 2091-9 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Cells, Cultured Cytokines / immunology, metabolism Dermatitis, Atopic / genetics*, immunology, pathology* Epidermis / immunology, metabolism, pathology Gene Expression* Gene Expression Profiling Humans Immunohistochemistry Interleukin-13 / immunology, metabolism* Interleukin-4 / immunology, metabolism* Keratinocytes / immunology, metabolism, pathology Microscopy, Electron, Transmission Organ Culture Techniques Phosphorylation STAT6 Transcription Factor / metabolism Th2 Cells / immunology, metabolism Tissue Engineering / methods* |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Interleukin-13; 0/STAT6 Transcription Factor; 207137-56-2/Interleukin-4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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