A SET OF INDUCIBLE GENES EXPRESSED BY ACTIVATED HUMAN MONOCYTIC AND ENDOTHELIAL-CELLS CONTAIN KAPPA-B-LIKE SITES THAT SPECIFICALLY BIND C-REL-P65 HETERODIMERS

NF-kappa B/Rel proteins regulate the inducible expression of many gene s in activated monocytes and endothelial cells that contain decameric kappa B and kappa B-like binding sites. In this study, we examined the binding of c-Rel-p65 heterodimers to non-consensus kappa B-like sites from several genes that do not bind prototypic NF-kappa B(p50-p65). c -Rel-p65 heterodimers from both monocytic and endothelial cells bound to the kappa B-Like sites in the interleukin-8, granulocyte/macrophage colony-stimulating factor, intercellular adhesion molecule-1, and tis sue factor genes but not to a closely related sequence in the granuloc yte colony-stimulating factor gene. In contrast, kappa B sites in the endothelial-leukocyte adhesion molecule-1 and Ig kappa genes that matc h the kappa B consensus, 5'-GGGRN-NYYCC-3' (where R indicates A or G, Y indicates C or T, and N indicates any base), bound NF-kappa B(p50-p6 5). Comparison of the kappa B-like sites indicated that c-Rel-p65 hete rodimers bound to a consensus sequence, 5'-HGGAR-NYYCC-3' (where R ind icates A or G, Y indicates C or T, H indicates A, C, or T, and N indic ates any base), which differs at position 1 from the kappa B consensus established for binding NF-kappa B(p50-p65) and other members of the NF-kappa B/Rel family. The selective binding of c-Rel-p65 heterodimers to kappa B-like sites in this set of genes may play a central role in regulating inducible gene expression in monocytes and endothelial cel ls.