Activation of NF‐κB 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‐ κ 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‐ κ B activation in response to some stimuli. Treatment of J558L cells with either TNF or lipopolysaccharide (LPS) resulted in nuclear translocation of NF‐ κ B, as demonstrated by electrophoretic mobility shift assay. Both TNF and LPS activated the same NF‐ κ B nuclear complexes, composed of the p50 and p65 subunits. LPS mediated a stronger and more sustained activation of NF‐ κ B than TNF. In contrast, TNF induced higher levels of H‐2 antigen surface expression than did LPS, suggesting that activation of NF‐ κ B is not sufficient for optimal enhancement of H‐2 expression. An inhibitor of NF‐ κ B activation, pyrrolidinedithiocarbamate (PDTC), dramatically reduced the induction of H‐2 antigen by TNF, supporting the view that NF‐ κ 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‐ κ B also decreased after PDTC treatment. However, PDTC had a smaller inhibitory effect on LPS‐induced NF‐ κ B activation and H‐2 antigen expression, suggesting that TNF and LPS activate NF‐ κ B by somewhat different pathways. J. Leukoc. Biol . 55: 7–12; 1994.