Tumor necrosis factor receptor p75 mediates cell-specific activation of nuclear factor kappa B and induction of human cytomegalovirus enhancer.
The functional role of human tumor necrosis factor receptor (TNFR) p75 was studied by the use of TNFR p75-specific agonistic antibodies. Human SW480T adenocarcinoma cells, stably transfected with a reporter construct containing beta-galactosidase under the control of human cytomegalovirus immediate early enhancer, were stimulated with anti-TNFR p75 polyclonal antiserum or monoclonal antibodies followed by measurement of beta-galactosidase activity and analysis by electrophoretic mobility shift assays. It was found that cross-linking of TNFR p75 led to strong induction of the human cytomegalovirus enhancer as well as activation of nuclear factor-kappa B (NF-kappa B). Stimulation of TNFR p75 also mediated activation of NF-kappa B in human KYM-1 rhabdomyosarcoma cells but not in other cell types such as U937 and HL-60 monocytic cells or in Eahy 926 endothelial cells. NF-kappa B activation induced by TNFR p75 was delayed approximately 15 min compared with NF-kappa B activation induced by TNFR p55, indicating that the two TNFRs activate NF-kappa B through different signaling pathways. The data presented in this study identify intracellular responses mediated by TNFR p75 which have not been reported previously and suggest that TNFR p75-induced activation of NF-kappa B is strictly cell type-specific.
Laegreid
A
A
Institute of Cancer Research, University of Trondheim, Norway.
Medvedev
A
A
Nonstad
U
U
Bombara
M P
MP
Ranges
G
G
Sundan
A
A
Espevik
T
T
D001483:Base Sequence; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D003587:Cytomegalovirus / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D018124:Receptors, Tumor Necrosis Factor