title: High-resolution transcriptional profiling of chemical-stimulated dendritic cells identifies immunogenic contact allergens, but not prohaptens.
abstract: Allergic contact dermatitis is a complex syndrome and knowledge about the in vitro detection of small-molecular-weight compounds, particularly prohaptens, is limited. Therefore, we investigated chemical-induced gene expression changes in human antigen-presenting cells upon stimulation with immunogenic contact allergens, prohaptens and irritants. Monocyte-derived dendritic cells (moDCs) and THP-1 cells were stimulated with the prohapten cinnamic alcohol (CAlc), the hapten cinnamic aldehyde (CAld), an irritant and an obligatory sensitizer in vitro. Whole-genome screening and consecutive PCR analysis of differential gene expression in moDCs stimulated with either CAld or the obligatory sensitizer revealed coregulation of 11 marker genes which were related to immunological reactions (IL-8, CD1e, CD200R1, PLA2G5, TNFRSF11A), oxidative or metabolic stress responses (AKR1C3, SLC7A11, GCLM) or other processes (DPYLS3, TFPI, TRIM16). In contrast, the prohapten CAlc and the irritant did not change marker gene expression. In THP-1 cells, CAld and the positive control elicited similar expression changes in only 4 of the previously identified genes (IL-8, TRIM16, CD200R1, GCLM). In conclusion, we provide important insights into the pathophysiological basis of allergic contact dermatitis, identify marker genes suitable for skin hazard assessment and demonstrate that contact-allergenic prohaptens escape in in vitro detection if their skin metabolism is not taken into account.
authors.affiliation: Department of Dermatology and Allergology, RWTH Aachen University Hospital, Aachen, Germany. hagen.ott @ post.rwth-aachen.de
authors.forename: H
authors.initials: H
authors.lastname: Ott
authors.forename: T
authors.initials: T
authors.lastname: Wiederholt
authors.forename: M Andresen
authors.initials: MA
authors.lastname: Bergström
authors.forename: R
authors.initials: R
authors.lastname: Heise
authors.forename: C
authors.initials: C
authors.lastname: Skazik
authors.forename: K
authors.initials: K
authors.lastname: Czaja
authors.forename: Y
authors.initials: Y
authors.lastname: Marquardt
authors.forename: A-T
authors.initials: AT
authors.lastname: Karlberg
authors.forename: H-F
authors.initials: HF
authors.lastname: Merk
authors.forename: J M
authors.initials: JM
authors.lastname: Baron
mesh_terms: D000485:Allergens / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling / Q000379:methods*; D006241:Haptens / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D020005:Propanols / Q000276:immunology* / Q000633:toxicity
chemical_list: D000485:Allergens; D006241:Haptens; D020005:Propanols; C020722:cinnamyl alcohol