Send to:

Choose Destination
See comment in PubMed Commons below
Circulation. 2002 Nov 19;106(21):2707-13.

E2F-1 regulates nuclear factor-kappaB activity and cell adhesion: potential antiinflammatory activity of the transcription factor E2F-1.

Author information

  • 1Wafic Said Gene Therapy Research Laboratory, Texas Heart Institute and Department of Medicine, University of Texas-Houston Medical School, Houston, Tex 77030, USA.



The transcription factor E2F-1 promotes vascular smooth muscle cell apoptosis and is reported to inhibit apoptosis induced by tumor necrosis factor (TNF)-alpha in endothelial cells. Whether E2F-1 overexpression exerts potentially antiinflammatory effects in endothelial cells is not known.


By immunoblotting and immunofluorescence, TNF-alpha treatment of human aortic endothelial cells (HAECs) with the control vector Ad.null was followed by rapid nuclear translocation of nuclear factor (NF)-kappaB p65, whereas nuclear translocation of p65 was markedly reduced in HAECs overexpressing E2F-1. Electrophoretic mobility shift assay and gel shift analysis of nuclear cell extracts confirmed that HAECs treated with a recombinant adenovirus encoding E2F-1 failed to associate with the binding domain of p65. Stimulation of the Ad.null-infected endothelial cells with TNF-alpha resulted in enhanced expression of endothelial intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and E-selectin and enhanced adhesion of monocytic U937 cells to the HAECs. Adhesion molecule expression and cell adhesion were reduced in E2F-1-transduced HAECs, associated with a marked decrease in phosphorylated IkappaB-alpha, required for nuclear translocation of NF-kappaB p65.


These findings suggest that E2F-1 stabilizes IkappaB and thereby may inhibit NF-kappaB-dependent processes involved in atherogenesis, including endothelial expression of E-selectin, vascular cellular adhesion molecule-1, and intracellular adhesion molecule-1 and cell adhesion to perturbed endothelial cells.

Comment in

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk