Hsu S C, Gavrilin M A, Lee H H, Wu C C, Han S H, Lai M Z
Graduate Institute of Microbiology, National Taiwan University School of Medicine, Taipei, Taiwan.
Eur J Immunol. 1999 Sep;29(9):2948-56. doi: 10.1002/(SICI)1521-4141(199909)29:09<2948::AID-IMMU2948>3.0.CO;2-0.
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 FasL. cAMP inhibited activation-induced apoptosis by an effective suppression of TCR-coupled FasL expres sion. 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 FasL promoter, the activation of NF-kappaB, but not of NF-AT and AP-1, was suppressed by cAMP. The prominent role of NF-kappaB was further demonstrated by a better activation of the FasL promoter and an elevated expression of FasL induced by p65 (RelA) overexpression than those induced by AP-1 or NF-AT. Our results demonstrate the essential role of NF-kappaB for the expression of the death receptor ligand FasL, and suggest a direct link between NF-kappaB activation and the expression of FasL. NF-kappaB may be the common mediator in the induction of FasL through TCR activation and by various stress stimuli.
淋巴细胞的凋亡是由不同刺激通过诱导Fas和Fas配体（FasL）的表达而触发的。以T细胞活化诱导的Fas/FasL表达作为模型系统，我们观察到Fas和FasL诱导的差异调节。cAMP通过有效抑制TCR偶联的FasL表达来抑制活化诱导的凋亡。相反，cAMP对活化诱导的Fas表达干扰较弱，cAMP处理的T细胞上剩余的Fas分子仍介导凋亡。在FasL启动子上的主要转录元件中，cAMP抑制NF-κB的活化，但不抑制NF-AT和AP-1的活化。p65（RelA）过表达诱导的FasL启动子活化和FasL表达升高比AP-1或NF-AT诱导的更显著，进一步证明了NF-κB的重要作用。我们的结果证明了NF-κB在死亡受体配体FasL表达中的重要作用，并提示NF-κB活化与FasL表达之间存在直接联系。NF-κB可能是通过TCR活化和各种应激刺激诱导FasL的共同介质。
