The innate immune system plays an important role as a first defense against pathogens and involves the recognition of bacteria and viruses, and byproducts thereof, by Toll receptors on immunecompetent cells (1). Activated cells synthesize and secrete cytokines, which in turn activate systemic responses directed at clearing the pathogen. Two important cytokines are interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α). These cytokines, as well as the Toll receptors, initiate intracellular signaling cascades that activate nuclear factor κB (NF-κB), activator protein-1 (AP-1), and cAMP responsive element binding proteins (CREBs), which are transcription factors essential for the regulation of numerous genes, many of which play important roles in immunological processes. Subunits of the AP-1 and the CREB protein families may form both homo-and heterodimers; the latter may comprise subunits both from within and between protein families. The signaling pathways leading to activation of at least NF-κB and AP-1 are common proximal to the receptors but diverge downstream to provide specificity (2). A common tool for examining signaling cascades is the luciferase (or chloramphenicol acetyltransferase) reporter assay. Such assays offer advantages such as simple protocols, no requirement for highly efficient transfections, and the possibility of elucidating molecular orders of signaling factors and determining branch-points of diverging signaling cascades. The endothelial leukocyte-adhesion molecule (ELAM)-1 (also called E-selectin) promoter contains three NF-κB sites, two of which are partially overlapping, that have been reported to be required for full induction by cytokines. A putative AP-1 site at position-499 to-493 within the promoter has been shown not to affect cytokine induction (3). Consequently, this promoter is often used to drive expression of luciferase in reporter assays and is frequently considered to be an “NF-κB-specific” promot-