Figure 5

IL-17-mediated-RAGE induction in RA-FLS involves PI3kinase, STAT3, NF-kB and AP-1. RA-FLS were pretreated with 50 μM AG490 or 10 μM parthenolide for 30 minutes, and then 10 ng/ml IL-17 was added for 12 h. RA-FLS were cultured with 10 ng/ml IL-17. The protein levels of phosphoSTAT3, phosphoIkB, phosphoC-Jun, and phosphoAKT were analyzed by Western blot. The expression of phosphoSTAT3, phosphoIkB, phosphoC-Jun, and phosphoAKT on FLS was assessed by immunohistochemical staining using specific antibodies. Co-immunostaining of RAGE and phospho STAT3, phospho IκB, phospho c-Jun, and phospho AKT showed the link between in vitro signaling molecules and RAGE. Values are the mean ± SEM of triplicate cultures. *P < 0.05, **P < 0.005 compared to IL-17 or inhibitor-treated cells.