|
Title
|
|
|
|
Functionality and specificity of gene markers for skin sensitization in dendritic cells
| |
|
Author
|
|
|
|
| |
|
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. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Toxicology letters. - Amsterdam
| |
|
Publication
|
|
|
|
Amsterdam
:
2011
| |
|
ISSN
|
|
|
|
0378-4274
| |
|
Volume/pages
|
|
|
|
203
:2
(2011)
, p. 106-110
| |
|
ISI
|
|
|
|
000291140400002
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|