A specific p38 inhibitor and a dominant negative MKK6 allele inhibit IL-12–induced STAT4 transcriptional activity.

(A), SB202190 inhibits IL-12–dependent, STAT4-mediated transactivation. NIH3T3 cells were transiently transfected with the p3xGAS-luc and the pCMV-β-galactosidase reporters, together with expression vectors encoding the human IL-12R subunits. Where indicated, cells were cotransfected with control vector (EV) or wild-type STAT4. As indicated, the cells were pretreated with DMSO or SB202190 for 1 hour before IL-12 stimulation. The experiment was performed as described in Figure 1C. (B), MKK6KR inhibits IL-12–dependent, STAT4-mediated transactivation. NIH3T3 cells were transiently transfected with 0.1 μg p3xGAS-luc reporter, along with 0.1 μg pCMV-β-galactosidase reporter, 0.1 μg pEFBOS-IL-12Rβ1, and 0.3 μg pEFBOS-IL-12Rβ2. Where indicated, cells were cotransfected with control vector (EV), 0.1 μg wild-type STAT4, 1.1 μg MKK6KR, or 0.5 μg MEKAA. The experiment was performed as described in Figure 1C.