title: Active transport of contact allergens in human monocyte-derived dendritic cells is mediated by multidrug resistance related proteins.
abstract: The multidrug resistance related proteins (MRPs) function as efflux transporters of a variety of large organic anions or their conjugates. In recent studies we demonstrated that antigen-presenting cells express a specific pattern of MRPs. MRP-mediated efflux activity of human monocyte-derived dendritic cells (moDCs) was analyzed using an in vitro transport assay. The efflux transport of radiolabeled contact allergens was inhibited using the specific MRP inhibitor indomethacin. Treatment with indomethacin increased intracellular concentration of [³H] eugenol and [³H] isoeugenol in moDCs. In addition by using MRP1 expressing inside-out membrane vesicles we revealed that the transport of eugenol is mediated by MRP1. Human DCs were employed to assess the sensitizing potential of contact allergens and alters their cytokine gene expression profile. Hence, to survey the functionality of indomethacin after stimulation with contact allergens IL-8 and TRIM16 regulation was measured by a DC-based in vitro assay. Incubation with isoeugenol after pre-treatment with indomethacin leads to increased IL-8 and TRIM16 gene expression. These results strongly support the functional role of MRPs in the active efflux of contact allergens also in antigen-presenting cells like moDCs, a novel mechanism which could possibly play a role in the pathogenesis of contact allergy.
authors.affiliation: Department of Dermatology and Allergology, University Hospital, RWTH Aachen University, Pauwelsstraße 30, D-52074 Aachen, Germany. cskazik@ukaachen.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Skazik
authors.forename: Ruth
authors.initials: R
authors.lastname: Heise
authors.forename: Hagen
authors.initials: H
authors.lastname: Ott
authors.forename: Katharina
authors.initials: K
authors.lastname: Czaja
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Marquardt
authors.forename: Hans F
authors.initials: HF
authors.lastname: Merk
authors.forename: Jens M
authors.initials: JM
authors.lastname: Baron
mesh_terms: D000485:Allergens / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005054:Eugenol / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000485:Allergens; D005054:Eugenol; D007213:Indomethacin; D027425:ATP-Binding Cassette, Sub-Family C Proteins