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Fig. 3. Effect of the inhibition of p38 and JNK on Fas-mediated apoptosis. Jurkat cells were incubated with Fas-mAb (150 ng/ml) in the absence and presence (15 µM) of SP600125 and/or p38 inhibitors for 4 hours. (A) Fas-signaled apoptosis (lane 2) was enhanced 2.8-fold by PD169316 (lane 3) and 4-fold by SP600125 (lane 4). (B) The reduction in mitochondrial membrane potential ( ${Delta}$ ${Psi}$ _m) in cells undergoing Fas-mediated apoptosis (lane 2) was enhanced by SP600125 (lane 4) but not PD169316 (lane 3). PD169316 suppressed the sensitizing effect of SP600125 (lane 5). These inhibitors by themselves (individually or together) did not trigger apoptosis or decrease of ${Delta}$ ${Psi}$ _m (lanes 6-8). The sensitizing effect of SP600125 on Fas-induced apoptosis (panel C) and the reduction in ${Delta}$ ${Psi}$ _m (panel D) was abrogated by two other p38 inhibitors SB203580 and SB202190 but not by the inactive derivative SB202474 (mean±s.e.m., n=12).

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