| IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. | |
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MedLine Citation:
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PMID: 22229441 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Atopic eczema and psoriasis are common skin diseases. While it is well established that the pathogenesis of these diseases varies, both are characterized by impairment in epidermal barrier function and abnormal IL-17 expression in the skin and peripheral blood. Recent findings indicated that filaggrin is essential during barrier formation and its insufficiency underlies the pathogenesis of atopic eczema. Filaggrin downregulation has also been reported in psoriasis. It is clear that Th1/Th2 bias influences expression of the protein, but an analysis of the effects of interleukin-17 (IL-17) on the expression of the protein and profilaggrin-processing enzymes has not yet been reported. In addition, the effect of the cytokine on components of functional epidermal barrier, tight junctions and adhesion/desmosomal proteins, has not been elucidated. Keratinocytes were exposed to interleukin-17A, and microarray analysis was performed. Filaggrin protein level was assessed by western blot. We have observed a significant decrease in profilaggrin mRNA level in interleukin-17A-exposed cultures (P = 0.008). Expression of processing enzymes was also altered, indicating an indirect effect of the cytokine on filaggrin production/degradation. Moreover, expression of many genes involved in cellular adhesion was also decreased. A significant downregulation of filaggrin at the protein level was detected by western blot in immortal and primary keratinocytes. Gene ontology analysis indicated changes in keratinization, epidermal differentiation and formation of the cornified envelope. We conclude that IL-17A downregulates the expression of filaggrin and genes important for cellular adhesion which could affect epidermal barrier formation. This effect potentially contributes to barrier dysfunction and could become a possible therapeutic target. |
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Authors:
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Danuta Gutowska-Owsiak; Anna L Schaupp; Maryam Salimi; Tharini A Selvakumar; Tess McPherson; Stephen Taylor; Graham S Ogg |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Experimental dermatology Volume: 21 ISSN: 1600-0625 ISO Abbreviation: Exp. Dermatol. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9301549 Medline TA: Exp Dermatol Country: Denmark |
Other Details:
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Languages: eng Pagination: 104-10 Citation Subset: IM |
Copyright Information:
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© 2011 John Wiley & Sons A/S. |
Affiliation:
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MRC Human Immunology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK Translational Gastroenterology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK Computational Biology Research Group, University of Oxford, John Radcliffe Hospital, Oxford, UK. |
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