Synergistic and antagonistic effects of ERK1/2 and p38 MAPKmodulate MoDC migration and cytokine secretion. MoDCs were stimulated as described in the legend to Figure 1. Additionally, PD98059 (inhibitor of ERK1/2) or p38 MAPK inhibitor (p38i) was added as indicated. Cellular lysates were prepared after 2 and 24 hours. (A) Inhibition of phosphorylation of the p38K substrates MAPKAPK-2 and hsp-27 but not of p38K by 10 μM p38K inhibitor (p38Ki). One representative of at least 3 experiments is shown. (B) Inhibition of ERK1/2 phosphorylation but not of p38K phosphorylation by the MEK inhibitor PD98059. One representative of at least 5 experiments is shown. (C) Inhibition of migration of MoDCs activated for 48 hours with the indicated protocols by p38Ki (10 μM) (mean ± SEM of 4 to 8 experiments, **P < .01). (D) Enhanced migration of MoDCs activated for 48 hours in the presence of PD98059 (30 μM) (mean ± SEM of 4 to 8 experiments, *P < .05). (E) Reduction of IL-6 secretion and (F) reduction of IL-12p70 secretion by MoDCs activated with intact E coli for 48 hours in the absence or presence of p38Ki (10 μM), PD98059 (30 μM), or both (mean ± SEM of 7 experiments, *P < .05, **P < .01).