text: Inhibition of IL-17 production by signal transduction inhibitors and anti-rheumatic drugs
  Having observed the increased IL-17 production in RA PBMC, it was important to know which signal transduction pathways were involved. As illustrated in Fig. 3, an significant decrease in anti-CD3-induced IL-17 production was observed when co-incubated with NF-kappaB inhibitor, PDTC and dexamethasone in comparison with anti-CD3 alone (38 +/- 5 and 54 +/- 11 versus 98 +/- 19 pg/ml, respectively; P < 0.05). 
  LY294002 and wortmannin, as an inhibitor of PI3K, also markedly inhibited the anti-CD3-induced IL-17 production in RA PBMC (98 +/- 19 versus 38 +/- 10 pg/ml [P < 0.005] and 48 +/- 4 pg/ml [P < 0.05], respectively). 
  The calcineurin inhibitors cyclosporin A and FK506 also downregulated the IL-17 secretion as well as the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 did, whereas rapamycin and PD98059 had no effect on IL-17 levels (Fig. 3). To evaluate the possibility of non-specific inhibition by the drug at high concentrations, we observed the dose response of PDTC and LY294002 for the inhibition of IL-17 production in PBMC. There were dose-dependent inhibitions of IL-17 production with chemical inhibitors (Fig. 4a). The other inhibitors in addition to PDTC and LY294002 showed the same pattern of inhibition. Cytotoxic effects on PBMC by the chemical inhibitors at experimental concentrations were not observed (Fig. 4b). 
  