Kasibhatla S, Genestier L, Green D R
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
J Biol Chem. 1999 Jan 8;274(2):987-92. doi: 10.1074/jbc.274.2.987.
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.
T细胞受体的结合可激活对细胞因子基因调控至关重要的转录因子。此外，该信号通路还会导致T淋巴细胞中依赖FasL转录和表达的激活诱导凋亡。在此我们证明，参与活化淋巴细胞中许多细胞因子基因转录调控的核因子κB（NF-κB），在T细胞活化诱导的FasL表达中也发挥作用。抑制T细胞杂交瘤中的NF-κB活性会导致T细胞受体刺激后FasL表达降低和凋亡。我们确定了FasL启动子中有助于这种调控的NF-κB位点。p65（Rel A）与FasL启动子共表达增强了其活性，而IκB的共表达则显著抑制了诱导型启动子活性。相反，转录因子AP-1对于激活诱导的FasL启动子活性并非必需。这些结果确定了NF-κB在介导T细胞活化过程中FasL表达方面的作用。
