title: The sensitizers nickel sulfate and 2,4-dinitrofluorobenzene increase CD40 and IL-12 receptor expression in a fetal skin dendritic cell line.
abstract: Dendritic cells (DCs) are antigen-presenting cells (APCs) capable of capturing haptens and to process and present them to T lymphocytes. In order to sensitize T cells for contact hypersensitivity (CHS), skin DCs suffer a maturation process with modifications on their surface molecules. The aim of this work was to evaluate changes induced by two contact sensitizers, 2,4-dinitrofluorobenzene (DNFB) and nickel sulfate (NiSO4), and a non-sensitizer 2,4-dichloronitrobenzene (DCNB), on the protein levels of two activation markers, CD40 and IL-12 receptor (IL-12R), in a mouse skin dendritic cell line (FSDC). The expression of CD40 and IL-12R proteins was evaluated by western blot assay and direct immunofluorescence microscopy. The results showed that CD40 and IL-12R expression increased significantly after cell exposure to NiSO4 and DNFB, although DNFB exhibited a stronger activity. There was no effect with DCNB. The epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), also used in the experiments, slightly increased the expression of both CD40 and IL-12R and when tested together with the sensitizers the effect was partially additive. The results suggest that the sensitizers DNFB and NiSO4 are directly involved on the changes of the surface markers CD40 and IL-12R in skin DCs, during the sensitization phase of CHS, and this effect may be enhanced by GM-CSF. In contrast, no effect was observed with DCNB.
authors.affiliation: Faculdade de Farmácia, Universidade de Coimbra, Rua do Norte, 3000-295, Coimbra, Portugal.
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Vital
authors.forename: Margarida
authors.initials: M
authors.lastname: Gonçalo
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cruz
authors.forename: Américo
authors.initials: A
authors.lastname: Figueiredo
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Duarte
authors.forename: Maria
authors.initials: M
authors.lastname: Celeste Lopes
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003877:Dermatitis, Contact; D004139:Dinitrofluorobenzene / Q000494:pharmacology*; D005333:Fetus / Q000033:anatomy & histology* / Q000502:physiology; D007509:Irritants / Q000494:pharmacology; D051379:Mice; D009532:Nickel / Q000494:pharmacology*; D018123:Receptors, Interleukin / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D012867:Skin / Q000166:cytology / Q000187:drug effects
chemical_list: D019013:CD40 Antigens; D007509:Irritants; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; C029938:nickel sulfate; D009532:Nickel; D004139:Dinitrofluorobenzene