p38 mitogen-activated protein kinase is involved in Fas ligand expression

p38 mitogen-activated protein kinase (MAPK) is activated by T cell receptor engagement. Here we showed that T cell receptor activated p38 alpha but not p38 delta, Inhibition of p38 alpha by the specific inhibitor SE 203580 prevented activation-induced cell death in T cells. SE 203580 had no effect on Fas-initiated apoptosis. Instead, SE 203580 preferentially inhibited activation-induced Fas ligand (FasL) expression. The inhibition on Fast expression by SE 203580 was correlated with the suppression on the Fast promoter activation. Overexpression of active MAPK kinase 3b, the activator of p38 MAPK, led to activation of Fast promoter and induction of Fast transcripts in T cells. Stress stimulation of T cells by anisomycin also induced Fast expression in a p38 MAPK-dependent manner, The induction of Fast expression in nonlymphoid cells such as 293T also required activation of p38 MAPK. Our results suggest that p38 MAPK is essential for FasL expression.