title: E2F-1 regulates nuclear factor-kappaB activity and cell adhesion: potential antiinflammatory activity of the transcription factor E2F-1.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wafic Said Gene Therapy Research Laboratory, Texas Heart Institute and Department of Medicine, University of Texas-Houston Medical School, Houston, Tex 77030, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Carrie
authors.initials: C
authors.lastname: Capps
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: Pierre
authors.initials: P
authors.lastname: Zoldhelyi
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha