Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells.
A critical step in the induction of allergic contact dermatitis is the interaction of haptens with immature dendritic cells (iDC) leading to their activation. Therefore iDC appear as suitable targets for the evaluation of the sensitizing properties of haptens with the aim of developing in vitro toxicologic methods. Here, using a low-density cDNA-array, we analyzed the expression of 165 genes related to dendritic cell biology in human iDC following a 24h incubation with four haptens representative of strong (DNBS), moderate (isoeugenol) and weak (eugenol, hydroxycitronellal) contact sensitizers and with one irritant sodium dodecyl sulphate (SDS). Results show that 21/165 iDC genes were significantly modulated by hapten treatment. Some genes were preferentially modulated by a given chemical. Thus, DNBS, isoeugenol, eugenol and hydroxycitronellal consistently modulated CCR5, CCL27, CCL2 and CCR7, respectively, whereas the CXCL10 gene was regulated by SDS. When subjected to principal component analysis, the 21 target genes fell into four groups associated with a particular type of chemical endowed with distinct sensitizing or irritant properties. Thus, gene profiling of iDC using low-density microarray allows, for screening of chemicals, the indentification of weak haptens with potential skin sensitizing properties. These results suggest that gene profiling of iDC using low-density microarrays may be useful to identify chemicals with weak skin sensitizing properties.
Cluzel-Tailhardat
M
M
LVMH Recherche, 185 avenue de Verdun, 45804 St Jean de Braye Cedex, France. mtailhardat@research.lvmh-pc.com
Bonnet-Duquennoy
M
M
de Queral
D Pelle
DP
Vocanson
M
M
Kurfürst
R
R
Courtellemont
P
P
Le Varlet
B
B
Nicolas
J-F
JF
D000485:Allergens / Q000633:toxicity*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000633:toxicity; D005054:Eugenol / Q000031:analogs & derivatives / Q000633:toxicity; D020869:Gene Expression Profiling; D006241:Haptens / Q000633:toxicity*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D013729:Terpenes / Q000633:toxicity
D000485:Allergens; D006241:Haptens; D013729:Terpenes; C045305:2,4-dinitrofluorobenzene sulfonic acid; D012967:Sodium Dodecyl Sulfate; D005054:Eugenol; C036643:isoeugenol; C020755:hydroxycitronellal; D004139:Dinitrofluorobenzene