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Title
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Functionality and specificity of gene markers for skin sensitization in dendritic cells
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Author
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Abstract
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| Transcriptomic analyses revealed a discriminating gene expression profile in human CD34+ progenitor-derived dendritic cells (DC) after exposure to skin sensitizers versus non-sensitizers. Starting from the differential expression in a small set of genes, a preliminary classification model (VITOSENS®) has been developed to identify chemicals as (non-)sensitizing. The objective of the current study is to gain knowledge on the role of the VITOSENS® markers in the DC maturation process, as well as to investigate their activation by a skin sensitizer versus a non-sensitizing danger molecule. To evaluate the functional relevance of VITOSENS® biomarkers in DC maturation, their response induced by the sensitizer dinitrofluorobenzene (DNFB) was pharmacologically counteracted. Flow cytometry analyses revealed that CD86 was down-regulated after COX2 inhibition, whereas expression of HLA-DR was reduced by stimulating CCR2. When exposing DC to DNFB versus lipopolysaccharide S (LPS), expression of most discriminating genes CREM and CCR2 was not altered by LPS as opposed to DNFB. To summarize, the observations in this research indicate that a selection of the VITOSENS® genes may be functionally involved in sensitizer-induced DC activation. By comparing their responsiveness towards a non-sensitizing danger signal and a sensitizer, VITOSENS® gene markers CREM and CCR2 appear to display a specific response. |
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Language
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English
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Source (journal)
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Toxicology letters. - Amsterdam
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Publication
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Amsterdam
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2011
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ISSN
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0378-4274
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DOI
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10.1016/J.TOXLET.2011.02.015
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Volume/pages
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203
:2
(2011)
, p. 106-110
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ISI
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000291140400002
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Full text (Publisher's DOI)
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