NF-kappa B-dependent Fas ligand expression.
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.
Hsu
S C
SC
Graduate Institute of Microbiology, National Taiwan University School of Medicine, Taipei, Taiwan.
Gavrilin
M A
MA
Lee
H H
HH
Wu
C C
CC
Han
S H
SH
Lai
M Z
MZ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000096:biosynthesis / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D053938:DNA Fragmentation / Q000276:immunology; D053222:Fas Ligand Protein; D016193:G1 Phase / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000276:immunology / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D019014:fas Receptor; D000242:Cyclic AMP