Immunomodulatory effects of therapeutic gold compounds. Gold sodium thiomalate inhibits the activity of T cell protein kinase C.

摘要: Previous studies have shown that the gold compounds, sodium thiomalate (GST) and auranofin (AUR), which are effective in treatment of rheumatoid arthritis, inhibit functional activities a variety cells, but biochemical basis their effect is unknown. In current studies, human T cell proliferation interleukin 2 production by Jurkat cells were inhibited GST or AUR at pharmacologically relevant concentrations. Because it has been documented protein kinase C (PKC) involved activation, capacity compounds to PKC partially purified from was assayed vitro. found dose-dependent manner, caused no significant inhibition The inhibitory on abolished 2-mercaptoethanol. To investigate regulation vivo, levels activity examined. Cytosolic decreased slowly concentration- time-dependent manner as result incubation with GST. ascertain whether translocation down-regulation, associated membrane cystosolic fractions evaluated after phorbol myristate acetate (PMA) stimulation incubated cells. Translocation markedly pretreatment for 3 d, PMA down-regulate not altered preincubation. impact GST-mediated downregulation examined analyzing PMA-stimulated phosphorylation CD3. Although preincubated exhibited an increased density CD3, gamma chain CD3 inhibited. Specificity suggested finding did alter mitogen-induced increases inositol trisphosphate Finally, mechanism GST-induced detail, using subspecies rat brain. type II more effectively than III PKC, also enzymatic isolated catalytic fragment PKC. could be explained competition phospholipid nonspecific interference substrate. These data suggest immunomodulatory effects may its activity.