Regulation of Fas-Ligand Expression during Activation-induced Cell Death in T Lymphocytes via Nuclear Factor κB

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摘要：

T cell receptor engagement activates transcription factors important for cytokine gene regulation. Additionally, this signaling pathway also leads to activation-induced apoptosis in T lymphocytes that is dependent on FasL transcription and expression. Here we demonstrate that nuclear factor kappaB (NF-kappaB), which is involved in the transcriptional regulation of many cytokine genes expressed in activated lymphocytes, also plays a role in T cell activation-induced FasL expression. Inhibition of NF-kappaB activity in a T cell hybridoma leads to decreased FasL expression and apoptosis upon T cell receptor stimulation. We identified the NF-kappaB site in the FasL promoter that contributes to such regulation. Co-expression of p65 (Rel A) with the FasL promoter enhanced its activity, and co-expression of IkappaB dramatically inhibited the inducible promoter activity. In contrast, the transcription factor AP-1 is not required for activation-induced FasL promoter activity. These results define a role for NF-kappaB in mediating FasL expression during T cell activation.

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关键词：

Humans T-Lymphocytes Jurkat Cells DNA NF-kappa B Membrane Glycoproteins Receptors, Antigen, T-Cell Base Sequence Oxidative Stress Fas Ligand Protein