Tumor necrosis factor (TNF) and interleukin 1 are known to initiate endothelial vascular cell adhesion molecule (VCAM)-1 transcription primarily by activating nuclear factor (NF)-κB, which translocates to the nucleus. In addition to two NF-κB elements found within the minimal cytokine-inducible VCAM-1 promoter, an interferon-related factor (IRF) element (IRF-1) has been identified close to the transcription initiation site, suggesting that cytokines that induce IRF-1 might affect VCAM-1 expression levels. We therefore investigated the effects of interferons (IFNs), which strongly induce IRF-1, on VCAM-1 transcription and expression. We show that IFN-α and -γ enhance TNF-induced VCAM-1 mRNA transcription and protein expression in human endothelial cells. IFN enhancement of TNF-induced expression is also seen using chloramphenicol acetyl transferase reporter genes linked to the minimal cytokine inducible VCAM-1 promoter. Nuclear IRF-1 is the molecular basis of IFN enhancement, because (a) IFN plus TNF–treated cells displayed increased nuclear IRF-1 levels and increased IRF-1 binding to the VCAM-1 promoter, compared with cells treated with TNF alone; (b) kinetics of nuclear IRF-1 levels correlated with VCAM-1 mRNA levels; (c) transfection with an IRF-1 construct substituted for IFN treatment; and (d) transfection with an expression construct encoding IRF-2, a competitive inhibitor of IRF-1, reduced TNF-induced VCAM-1 expression. Our experiments show that IFN amplifies TNF-induced VCAM-1 expression at the transcriptional level by an IRF-1–dependent pathway.
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15 June 1998
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June 15 1998
Interferon Enhances Tumor Necrosis Factor–induced Vascular Cell Adhesion Molecule 1 (CD106) Expression in Human Endothelial Cells by an Interferon-related Factor 1–dependent Pathway
Sonja Lechleitner,
Sonja Lechleitner
From the *Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, A-1090 Austria; the ‡Department of Dermatology, Goethe University, Frankfurt, Germany 60590; and the §Boyer Center of Molecular Biology, Yale University, New Haven, Connecticut 06536
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Jens Gille,
Jens Gille
From the *Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, A-1090 Austria; the ‡Department of Dermatology, Goethe University, Frankfurt, Germany 60590; and the §Boyer Center of Molecular Biology, Yale University, New Haven, Connecticut 06536
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David R. Johnson,
David R. Johnson
From the *Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, A-1090 Austria; the ‡Department of Dermatology, Goethe University, Frankfurt, Germany 60590; and the §Boyer Center of Molecular Biology, Yale University, New Haven, Connecticut 06536
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Peter Petzelbauer
Peter Petzelbauer
From the *Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, A-1090 Austria; the ‡Department of Dermatology, Goethe University, Frankfurt, Germany 60590; and the §Boyer Center of Molecular Biology, Yale University, New Haven, Connecticut 06536
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Sonja Lechleitner
From the *Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, A-1090 Austria; the ‡Department of Dermatology, Goethe University, Frankfurt, Germany 60590; and the §Boyer Center of Molecular Biology, Yale University, New Haven, Connecticut 06536
Jens Gille
From the *Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, A-1090 Austria; the ‡Department of Dermatology, Goethe University, Frankfurt, Germany 60590; and the §Boyer Center of Molecular Biology, Yale University, New Haven, Connecticut 06536
David R. Johnson
From the *Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, A-1090 Austria; the ‡Department of Dermatology, Goethe University, Frankfurt, Germany 60590; and the §Boyer Center of Molecular Biology, Yale University, New Haven, Connecticut 06536
Peter Petzelbauer
From the *Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Vienna, A-1090 Austria; the ‡Department of Dermatology, Goethe University, Frankfurt, Germany 60590; and the §Boyer Center of Molecular Biology, Yale University, New Haven, Connecticut 06536
Address correspondence to Peter Petzelbauer, Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Phone: 43-1-40400-7764; Fax: 43-1-408-1928; E-mail: [email protected]
Received:
September 24 1997
Revision Received:
March 03 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (12): 2023–2030.
Article history
Received:
September 24 1997
Revision Received:
March 03 1998
Citation
Sonja Lechleitner, Jens Gille, David R. Johnson, Peter Petzelbauer; Interferon Enhances Tumor Necrosis Factor–induced Vascular Cell Adhesion Molecule 1 (CD106) Expression in Human Endothelial Cells by an Interferon-related Factor 1–dependent Pathway . J Exp Med 15 June 1998; 187 (12): 2023–2030. doi: https://doi.org/10.1084/jem.187.12.2023
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