Activation of NF-kappa B may be necessary but is not sufficient for induction of H-2 antigens by TNF in J558L murine myeloma cells.
We have investigated the role of the transcription factor NF-kappa B in the induction of H-2 antigens by tumor necrosis factor (TNF) in murine J558L myeloma cells. An earlier report suggested that J558L cells may have a defect in NF-kappa B activation in response to some stimuli. Treatment of J558L cells with either TNF or lipopolysaccharide (LPS) resulted in nuclear translocation of NF-kappa B, as demonstrated by electrophoretic mobility shift assay. Both TNF and LPS activated the same NF-kappa B nuclear complexes, composed of the p50 and p65 subunits. LPS mediated a stronger and more sustained activation of NF-kappa B than TNF. In contrast, TNF induced higher levels of H-2 antigen surface expression than did LPS, suggesting that activation of NF-kappa B is not sufficient for optimal enhancement of H-2 expression. An inhibitor of NF-kappa B activation, pyrrolidinedithiocarbamate (PDTC), dramatically reduced the induction of H-2 antigen by TNF, supporting the view that NF-kappa B is required for TNF-induced H-2 antigen expression. Constitutive levels of H-2 antigen expression on the cell surface and of nuclear NF-kappa B also decreased after PDTC treatment. However, PDTC had a smaller inhibitory effect on LPS-induced NF-kappa B activation and H-2 antigen expression, suggesting that TNF and LPS activate NF-kappa B by somewhat different pathways.
Wolchok
J D
JD
Department of Microbiology, New York University Medical Center, New York 10016.
Goodman
A R
AR
Vilcek
J
J
D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D006183:H-2 Antigens / Q000096:biosynthesis*; D015793:HLA-B7 Antigen / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010954:Plasmacytoma / Q000276:immunology / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016207:Cytokines; D006183:H-2 Antigens; D015793:HLA-B7 Antigen; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid