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Kyungjae Kim, Shinha Han, Hyunyul Kim, Kwanghee Kim, Jeunghak Kwon, Chong-Kil Lee, Auranofin, immunosuppressive drug, inhibits the MHC class I and MHC class II pathway of antigen presentation in dendritic cells (B41), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Pages LB8–LB9, https://doi.org/10.4049/jimmunol.178.Supp.B41
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Abstract
Auranofin (AF) is an orally administered, gold-based, anti-arthritic agent that has been used as a drug for the treatment of rheumatoid arthritis since the late 1970s. The precise mechanism of its anti-arthritic action is unclear. Therefore, this study examined the ability of AF to immunomodulate the antigen presenting cells (APCs), dendritic cells (DCs). The DCs were cultured in the presence of AF and examined for their ability to present exogenous antigens in association with the major histocompatibility complexes (MHC). This study examined whether or not AF (5 ~ 40 μM/ml) can inhibit the cross-presentation of DCs. DC2.4 cells (H-2Kb) or bone marrow-derived DCs (BM-DCs) generated from the BM cells of C57BL/6 mouse (H-2Kb) were cultured in the presence of AF with OVA-microspheres, and the amount of OVA peptide-class I MHC complexes was measured by T cell hybridoma, B3Z, that recognizes the OVA (257–264 : SIINFEKL)-(H-2Kb) complex and expresses β-galactosidase. The inhibitory activity of AF appeared to be due not only to its ability to inhibit the phagocytic activity of DCs but also to suppress the expression of MHC molecules on DCs. AF decreased the level of IL-2 production when the effects of AF on CD4+ T cells were examined. The secretion of TNF-α, IL-1β and IL-6 was measured in cell supernatants using ELISA when RAW264.7 was exposed to AF for 24 hrs. AF decreased production and pro-inflammatory cytokine, TNF-α, IL-1β, IL-6 and nitric oxide (NO) in macrophages. These results provide an understanding of the mechanism of immunosuppressive activity and anti-inflammatory effects of AF in relation to their actions on APCs.
