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  • Title: Regulation of Fas-dependent activation-induced T cell apoptosis by cAMP signaling: a potential role for transcription factor NF-kappa B.
    Author: Ivanov VN, Lee RK, Podack ER, Malek TR.
    Journal: Oncogene; 1997 May 22; 14(20):2455-64. PubMed ID: 9188860.
    Abstract:
    TCR-mediated activation of T cell hybridomas induces programmed cell death by a Fas-dependent pathway. We now show that costimulation of 2B4 cells, in the absence or presence of transgenic Bcl-2, with anti-CD3 epsilon and forskolin, an activator of cAMP signaling, resulted in antagonism of Fas-dependent activation-induced cell death that was always accompanied by selective downregulation of the nuclear levels of NF-kappa B p65-p50 (RelA-p50) transcription factor. Forskolin not only inhibited activation-induced cell death and NF-kappa B activation, but also suppressed expression of Fas and Fas ligand (Fas-L). Furthermore, NF-kappa B p65 antisense oligonucleotide down-regulated nuclear levels of NF-kappa B, inhibited cell surface expression of Fas-L and apoptosis of 2B4. Collectively, these finding demonstrate a potential role of NF-kappa B in the regulation of activation-induced apoptosis in T lymphocytes.
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