Title
Functionality and specificity of gene markers for skin sensitization in dendritic cellsFunctionality and specificity of gene markers for skin sensitization in dendritic cells
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Vaccine & Infectious Disease Institute (VAXINFECTIO)
Department of Biomedical Sciences - other
Individual research BMW
Publication type
article
Publication
Amsterdam,
Subject
Biology
Human medicine
Source (journal)
Toxicology letters. - Amsterdam
Volume/pages
203(2011):2, p. 106-110
ISSN
0378-4274
ISI
000291140400002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
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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