Adenovirus-mediated overexpression of c-Jun and c-Fos induces intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in human endothelial cells

As distal targets and mediators of signal transduction pathways, activator protein-1 (AP-I), c-Jun, and c-Fos are among the primary regulators of genes involved in cell function, proliferation, and differentiation. By using adenovirus-mediated gene transfer, we show that overexpression of AP-I proteins directly causes coinduction of gene expression of an adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), and a chemokine, monocyte chemoattractant protein-1 (MCP-I), in human vascular endothelial cells (ECs). The AP-l-induced gene expression occurs through a mechanism independent of nuclear factor-kappa B, Because the induced expression of ICAM-1 and MCP-1 in ECs has been implicated in endothelial activation and a number of important vascular disorders, it is suggested that AP-I activation may play an important role in the pathogeneses of inflammation, angiogenesis, and atherogenesis.