Auranofin, an immunosuppressive drug, inhibits MHC class I and MHC class II pathways of antigen presentation in dendritic cells.
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.
Han
Shinha
S
Department of Pharmacy, Sahmyook University, Seoul 139-742, Korea.
Kim
Kwanghee
K
Song
Youngcheon
Y
Kim
Hyunyul
H
Kwon
Jeunghak
J
Lee
Young-Hee
YH
Lee
Chong-Kil
CK
Lee
Sang-Jin
SJ
Ha
Namjoo
N
Kim
Kyungjae
K
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006183:H-2 Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects
D018501:Antirheumatic Agents; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D007166:Immunosuppressive Agents; C110366:OVA-8; D010446:Peptide Fragments; D015847:Interleukin-4; D001310:Auranofin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin