Auranofin, an immunosuppressive drug, inhibits MHC class I and MHC class II pathways of antigen presentation in dendritic cells
| Autor: | Young Hee Lee, Youngcheon Song, Nam-Joo Ha, Hyunyul Kim, Kyungjae Kim, Jeunghak Kwon, Kwanghee Kim, Shinha Han, Sang Jin Lee, Chong-Kil Lee |
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| Rok vydání: | 2007 |
| Předmět: |
Ovalbumin
Antigen presentation Down-Regulation chemical and pharmacologic phenomena Cell Line Mice Phagocytosis Auranofin Drug Discovery MHC class I Cytotoxic T cell Animals Antigen-presenting cell Cells Cultured MHC class II Antigen Presentation Mice Inbred BALB C biology Dose-Response Relationship Drug Antigen processing Organic Chemistry Histocompatibility Antigens Class I H-2 Antigens Histocompatibility Antigens Class II Cross-presentation Granulocyte-Macrophage Colony-Stimulating Factor Dendritic Cells MHC restriction Peptide Fragments Mice Inbred C57BL Antirheumatic Agents Immunology biology.protein Molecular Medicine Interleukin-4 Immunosuppressive Agents |
| Zdroj: | Archives of pharmacal research. 31(3) |
| ISSN: | 0253-6269 |
| Popis: | Auranofin (AF), an orally administered, gold-based, anti-arthritic agent, has emerged as a clinically useful therapeutic drug for the treatment of rheumatoid arthritis. In the present study, we examined the effects of AF on major histocompatibility complex (MHC)-restricted antigen presentation in dendritic cells (DCs), which are the most important accessory cells for the induction of T cell responses. A mouse dendritic cell line, DC2.4 cells, and DCs that were generated from mouse bone marrow cells by culturing with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 were each pretreated with AF for 2 hr, and then incubated with ovalbumin (OVA). After the 2-hr incubation, the DCs were fixed, and the amounts of OVA peptide-H-2Kb complexes were assessed using OVa-specific CD8+ T cells. AF inhibited MHC class I-restricted presentation of exogenous OVA. This inhibitory activity of AF appeared to be due not only to the inhibition of the phagocytic activity of DCs, but also to the suppression of MHC molecule expression on DCs. AF also inhibited MHC class II-restricted presentation of exogenous OVA. These results show that AF exerts immunosuppressive activity at least in part by inhibiting MHC-restricted antigen presentation in professional antigen-presenting cells. |
| Databáze: | OpenAIRE |
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