NF-κB-dependent Fas ligand expression

Apoptosis of lymphocytes is triggered by different stimuli through the induced expression of Fas and Fas ligand (FasL). Using T cell activation-induced Fas/FasL expression as a model system, we observed a differential regulation of the induction of Fas and Fast. cAMP inhibited activation-induced apoptosis by an effective suppression of TOP-coupled Fast expression. In contrast, cAMP weakly interfered with activation-induced Fas expression, and the remaining Fas molecules on cAMP-treated T cells still mediated apoptosis. Among the major transcription elements on the Fast promoter, the activation of NF-kappa B, but not of NF-AT and AP-I, was suppressed by cAMP. The prominent role of NF-kappa B was further demonstrated by a better activation of the Fast promoter and an elevated expression of Fast induced by p65 (ReIA) overexpression than those induced by AP-I or NF-AT. Our results demonstrate the essential role of NF-kappa B for the expression of the death receptor ligand Fast, and suggest a direct link between NF-kappa B activation and the expression of Fast. NF-kappa B may be the common mediator in the induction of Fast through TCR activation and by various stress stimuli.