Identification of proteins differentially expressed in dendritic cells upon exposure to contact allergens

德语. Allergic contact dermatitis is an unpleasant, sometimes even painful disease of great clinical relevance. Contact sensitizers are low molecular weight compounds that activate antigen-presenting dendritic cells (DCs) in the skin (so-called Langerhans cells, LCs) and thus a delayed-type immune response can occur. Our approach was to identify putative biomarkers of high predictive value in separating contact allergens from irritants and in reflecting their allergenic potency. As recently shown some of these compounds can induce activation of the Keap1-Nrf2-ARE signaling pathway, one major cytoprotective pathway in cells stressed by chemicals or oxidants. In our studies we used the well characterized monocytic THP-1 cell line as surrogate for LCs. Through immunoblotting we were able to confirm that known contact allergens such as cinnamic aldehyde (CA) and 1-chloro-2,4-dinitrobenzene (DNCB), but no irritants such as Sodium Dodecyl Sulfate (SDS), triggered the activation of Nrf2 and subsequent expression of its target genes in THP-1 cells. We found a time- and dose-dependent upregulation of heme oxygenase-1 (HO-1). Importantly, moderate doses of CA (i.e. 20 ìM) caused only a temporal increase in HO-1 protein levels, while higher oncentrations (i.e. 40 ìM) that still lacked significant cytotoxicity, led to a steadily increasing HO-1 protein expression level over a 24 h period. Applying a proteomics based strategy we were able to identify several proteins that are significantly upregulated after treatment with CA, some of them known to be regulated through Nrf2. Currently we evaluate the significance of our results by analyzing cellular signaling pathways in primary human monocyte-derived LCs.