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-1), 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-1 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-1), in human vascular endothelial cells (ECs). The AP-1-induced gene expression occurs through a mechanism independent of nuclear factor-kappaB. 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-1 activation may play an important role in the pathogeneses of inflammation, angiogenesis, and atherogenesis.
Wang
N
N
Division of Biomedical Sciences, University of California, Riverside 92521, USA.
Verna
L
L
Hardy
S
S
Forsayeth
J
J
Zhu
Y
Y
Stemerman
M B
MB
D000256:Adenoviridae / Q000235:genetics*; D001665:Binding Sites; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000502:physiology
D018932:Chemokine CCL2; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1