Identification of gene expression changes induced by chemical allergens in dendritic cells: opportunities for skin sensitization testing.
Cellular changes within resident skin dendritic cells (DCs) after allergen uptake and processing are critical events in the acquisition of skin sensitization. Here we describe the development of a set of selection criteria to derive a list of potential target genes from previous microarray analyses of human peripheral blood-derived (peripheral blood mononuclear cells (PBMCs)-DCs) treated with dinitrobenzene sulfonic acid for predicting skin-sensitizing chemicals. Based on those criteria, a probing evaluation of the target genes has been conducted using an extended chemical data set, comprising five skin irritants and 11 contact allergens. PBMCs-DCs were treated for 24 hours with various concentrations of chemicals and in each instance the expression of up to 60 genes was examined by real-time PCR analysis. Consistent allergen-induced changes in the expression of many genes were observed and further prioritization of the targets was conducted by analysis of the same genes in DCs treated with non-sensitizing chemicals to determine their specificity for skin sensitization. Real-time PCR analyses of multiple chemical allergens, irritants, and non-sensitizers have identified 10 genes that demonstrate reproducibly high levels of selectivity, specificity, and dynamic range consistent with providing the basis for robust and sensitive alternative approaches for the identification of skin-sensitizing chemicals.
Gildea
Lucy A
LA
Central Product Safety Department, Miami Valley Innovation Center, The Procter & Gamble Company, Cincinnati, Ohio 45253-8707, USA. gildea.la@pg.com
Ryan
Cindy A
CA
Foertsch
Leslie M
LM
Kennedy
Jennifer M
JM
Dearman
Rebecca J
RJ
Kimber
Ian
I
Gerberick
G Frank
GF
D000485:Allergens / Q000276:immunology / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012882:Skin Tests / Q000379:methods*
D000485:Allergens; D001557:Benzenesulfonates; C007488:dinitrobenzenesulfonic acid