We identified that anti-CD3-induced IL-17 production in RA PBMC was significantly hampered by the PI3K inhibitor LY294002 and the NF-κB inhibitor PDTC to comparable levels of basal production without stimulation. We also found that anti-CD3-induced IL-17 production was downregulated by the addition of SB203580, a p38 MAPK inhibitor. It is interesting that a series of evidence supports crosstalk between NF-κB and p38. In myocytes, IκB kinase-β is activated by p38 [32], and the activated p38 can stimulate NF-κB by a mechanism involving histone acetylase p300/CREB-binding protein [33]. Our results revealed that p38 MAPK activation was not affected by LY294002, whereas NF-κB binding activity was decreased by LY294002, which provided the evidence for a p38 MAPK pathway independent of PI3K activation. The direct relationship between p38 and NF-κB for IL-17 production needs to be studied in future experiments.