Regulation of Fas-dependent activation-induced T cell apoptosis by cAMP signaling: a potential role for transcription factor NF-kappa B.
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.
Ivanov
V N
VN
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA.
Lee
R K
RK
Podack
E R
ER
Malek
T R
TR
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D005576:Colforsin / Q000494:pharmacology; D053222:Fas Ligand Protein; D019254:Genes, bcl-2 / Q000502:physiology*; D006825:Hybridomas; D008213:Lymphocyte Activation / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology*
D000906:Antibodies; D017252:CD3 Complex; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D014157:Transcription Factors; D019014:fas Receptor; D005576:Colforsin