P50 (NF-KAPPA-B1) IS UP-REGULATED IN LPS TOLERANT P388D1 MURINE MACROPHAGES

Cells of the murine macrophage cell line P388D1 express cell surface C D14 and respond to LPS (lipopolysaccharide) stimulation with the produ ction of TNF (tumor necrosis factor). When the cells are stimulated wi th LPS a second time then little TNF is produced, i.e. the cells are t olerant. Flow cytometry analysis demonstrates that this tolerance is n ot due to a downregulation of the CD14 cell surface receptor. Analysis of proteins binding to the -516 NF-kappa B motif of the murine TNF pr omoter reveals that constitutive p50p50 and LPS stimulation lead to mo bilization of a heterodimer consisting of p65/c-rel. In tolerant cells less of the p65/c-rel heterodimer is mobilized but there is a strong upregulation of p50p50. These data show that tolerance to LPS in murin e macrophages may involve a predominance of p50 homodimers.