Regulation of Fas-dependent activation-induced T cell apoptosis by cAMP signaling: A potential role for transcription factor NF-κB

Vladimir N. Ivanov, Richard K. Lee, Eckhard R Podack, Thomas R. Malek

Research output: Contribution to journalArticle

67 Scopus citations

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-CD3ε and forskolin, an activator of cAMP signaling, resulted in antagonism of Fas-dependent activation-induced cell death that was always accompanied by selective down-regulation of the nuclear levels of NF-κB p65-p50 (RelA-p50) transcription factor. Forskolin not only inhibited activation-induced cell death and NF-κB activation, but also suppressed expression of Fas and Fas ligand (Fas-L). Furthermore, NF-κB p65 antisense oligonucleotide down-regulated nuclear levels of NF-κB, inhibited cell surface expression of Fas-L and apoptosis of 2B4. Collectively, these finding demonstrate a potential role of NF-κB in the regulation of activation-induced apoptosis in T lymphocytes.

Original languageEnglish (US)
Pages (from-to)2455-2464
Number of pages10
JournalOncogene
Volume14
Issue number20
DOIs
StatePublished - Jul 8 1997

Keywords

  • Apoptosis
  • Fas ligand
  • NF-κB
  • T lymphocyte

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Regulation of Fas-dependent activation-induced T cell apoptosis by cAMP signaling: A potential role for transcription factor NF-κB'. Together they form a unique fingerprint.

  • Cite this