Published Online
on October 28, 2002

A more recent version of this article appeared on November 19, 2002

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Submitted on July 3, 2002
Revised on September 4, 2002
Accepted on September 9, 2002

E2F-1 Regulates Nuclear Factor-B Activity and Cell Adhesion. Potential Antiinflammatory Activity of the Transcription Factor E2F-1

Min Chen MD, Carrie Capps BS, James T. Willerson MD, and Pierre Zoldhelyi MD^*

From Wafic Said Gene Therapy Research Laboratory, Texas Heart Institute and Department of Medicine (M.C., J.T.W., P.Z.), University of Texas-Houston Medical School, Houston, Tex.

^* To whom correspondence should be addressed. E-mail: zoldhelyi{at}aol.com.

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

Methods and Results—By immunoblotting and immunofluorescence, TNF- treatment of human aortic endothelial cells (HAECs) with the control vector Ad.null was followed by rapid nuclear translocation of nuclear factor (NF)-B 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- 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 IB-, required for nuclear translocation of NF-B p65.

Conclusions—These findings suggest that E2F-1 stabilizes IB and thereby may inhibit NF-B-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.

Key words: endothelium • inflammation • cell adhesion molecules • apoptosis

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