The gold anti-rheumatic drug auranofin governs T cell activation by enhancing oxygen free radical production.
Gold-containing drugs continue to be used in the treatment of rheumatoid arthritis, but their mode of action remains unknown. One model to explain gold action is that gold-containing compounds can alter free radical production in cells of the immune system, but direct evidence for this hypothesis has been lacking. In this study we show that auranofin can enhance the rapid flux of reactive oxygen species (ROS), which accompanies phytohemagglutinin activation of peripheral blood T cells. Blocking this enhancement by the addition of antioxidants can reverse the functional effects of the drug on T cell responses, which we have previously demonstrated. These results provide strong experimental support for a model in which gold anti-rheumatics act by modulating ROS production. Furthermore, our experiments suggest that auranofin may be a useful tool to investigate the postulated role of ROS in the intra cellular T cell signaling pathway.
Vint
I A
IA
Department of Pharmacology, University College London, GB.
Foreman
J C
JC
Chain
B M
BM
D001310:Auranofin / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D005978:Glutathione / Q000037:antagonists & inhibitors; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D010835:Phytohemagglutinins; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D007376:Interleukin-2; D010835:Phytohemagglutinins; D017382:Reactive Oxygen Species; D008717:Methionine Sulfoximine; D001310:Auranofin; D019328:Buthionine Sulfoximine; D005978:Glutathione; D003676:Deferoxamine; D013936:Thymidine