The Development and Characterization of an In Vitro Model of Psoriasis

In this study, the phenotype of psoriatic keratinocytes and fibroblasts in reconstructed skin models was compared to those constructed from normal cells. Characterization of this model by immunohistochemistry showed that classical markers of keratinocyte differentiation exhibited similar patterns of...

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Bibliographic Details
Published in:	Journal of investigative dermatology Vol. 123; no. 5; pp. 892 - 901
Main Authors:	Barker, Carol L., McHale, Mark T., Gillies, Angela K., Waller, John, Pearce, David M., Osborne, Joy, Hutchinson, Peter E., Smith, Gill M., Pringle, James H.
Format:	Journal Article
Language:	English
Published:	Danvers, MA Elsevier Inc 01-11-2004 Nature Publishing Elsevier Limited
Subjects:	Adult Aged Antibody Specificity Biological and medical sciences Cells, Cultured Chemokine CXCL1 chemokine receptors Chemokines, CXC - genetics Chemokines, CXC - immunology cytokines Dermatology Female Gene Expression - immunology Humans Immunohistochemistry Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - immunology Interferon-gamma - genetics Interferon-gamma - immunology Interleukin-6 - genetics Interleukin-6 - immunology interleukin-8 Interleukin-8 - genetics Interleukin-8 - immunology keratinocyte pathology Keratinocytes - cytology Keratinocytes - physiology Male Medical sciences Middle Aged Organ Culture Techniques - methods organotypic skin equivalents Phenotype Psoriasis - immunology Psoriasis - pathology Psoriasis - physiopathology Psoriasis. Parapsoriasis. Lichen Receptors, Interleukin-8A - genetics Receptors, Interleukin-8A - immunology Receptors, Interleukin-8B - genetics Receptors, Interleukin-8B - immunology Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - immunology keratinocyte pathology chemokine receptors cytokines organotypic skin equivalents interleukin-8 Skin disease Anatomic pathology Angiogenic factor Psoriasis Dermatology chemokine receptors/cytokines/interleukin-8/keratinocyte pathology/organotypic skin equivalents Cytokine Keratinocyte Models Chemokine receptor In vitro Interleukin 8
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Summary:	In this study, the phenotype of psoriatic keratinocytes and fibroblasts in reconstructed skin models was compared to those constructed from normal cells. Characterization of this model by immunohistochemistry showed that classical markers of keratinocyte differentiation exhibited similar patterns of distribution in the psoriatic models to those derived from normal cells and generally reflected in vivo observations. Some crucial differences, however, were observed between normal and psoriatic models when pro-inflammatory gene expression and keratinocyte proliferation were investigated. Notably, the chemokine receptor CXCR2 was overexpressed in the psoriatic models, and, moreover, was localized to the granular layer of keratinocytes as seen in psoriasis in vivo. Pro-inflammatory genes (tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ], and interleukin 8 [IL-8]) were expressed at high levels in the psoriatic models, but were only minimally expressed in the normal models. Models derived from uninvolved psoriatic skin showed the same gene expression profile as those derived from involved skin along with an increased proliferation rate when compared to normal models. These results suggest that psoriatic individuals possess an inherent predisposition to develop the disease phenotype even in the absence of T cells. This study represents a comprehensive characterization of psoriatic human skin reconstructed in vitro, and demonstrates the potential of this model as a valuable tool in drug discovery.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-202X 1523-1747
DOI:	10.1111/j.0022-202X.2004.23435.x