Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lechleitner, Sonja, Gille, Jens, Johnson, David R., Petzelbauer, Peter
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212361/
https://www.ncbi.nlm.nih.gov/pubmed/9625761
_version_ 1782148675960569856
author Lechleitner, Sonja
Gille, Jens
Johnson, David R.
Petzelbauer, Peter
author_facet Lechleitner, Sonja
Gille, Jens
Johnson, David R.
Petzelbauer, Peter
author_sort Lechleitner, Sonja
collection PubMed
description 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.
format Text
id pubmed-2212361
institution National Center for Biotechnology Information
language English
publishDate 1998
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-22123612008-04-16 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 Lechleitner, Sonja Gille, Jens Johnson, David R. Petzelbauer, Peter J Exp Med Articles 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. The Rockefeller University Press 1998-06-15 /pmc/articles/PMC2212361/ /pubmed/9625761 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Lechleitner, Sonja
Gille, Jens
Johnson, David R.
Petzelbauer, Peter
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212361/
https://www.ncbi.nlm.nih.gov/pubmed/9625761
work_keys_str_mv AT lechleitnersonja interferonenhancestumornecrosisfactorinducedvascularcelladhesionmolecule1cd106expressioninhumanendothelialcellsbyaninterferonrelatedfactor1dependentpathway
AT gillejens interferonenhancestumornecrosisfactorinducedvascularcelladhesionmolecule1cd106expressioninhumanendothelialcellsbyaninterferonrelatedfactor1dependentpathway
AT johnsondavidr interferonenhancestumornecrosisfactorinducedvascularcelladhesionmolecule1cd106expressioninhumanendothelialcellsbyaninterferonrelatedfactor1dependentpathway
AT petzelbauerpeter interferonenhancestumornecrosisfactorinducedvascularcelladhesionmolecule1cd106expressioninhumanendothelialcellsbyaninterferonrelatedfactor1dependentpathway