Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI119648

Role of NFkappaB in the mortality of sepsis.

H Böhrer, F Qiu, T Zimmermann, Y Zhang, T Jllmer, D Männel, B W Böttiger, D M Stern, R Waldherr, H D Saeger, R Ziegler, A Bierhaus, E Martin, and P P Nawroth

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Böhrer, H. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Qiu, F. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Zimmermann, T. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Zhang, Y. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Jllmer, T. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Männel, D. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Böttiger, B. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Stern, D. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Waldherr, R. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Saeger, H. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Ziegler, R. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Bierhaus, A. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Martin, E. in: JCI | PubMed | Google Scholar

Department of Anesthesiology, Department of Medicine, and Department of Pathology, University of Heidelberg, D-69120 Heidelberg, Germany.

Find articles by Nawroth, P. in: JCI | PubMed | Google Scholar

Published September 1, 1997 - More info

Published in Volume 100, Issue 5 on September 1, 1997
J Clin Invest. 1997;100(5):972–985. https://doi.org/10.1172/JCI119648.
© 1997 The American Society for Clinical Investigation
Published September 1, 1997 - Version history
View PDF
Abstract

Binding activity for nuclear factor kappa B (NFkappaB) consensus probes was studied in nuclear extracts from peripheral blood mononuclear cells of 15 septic patients (10 surviving and 5 not surviving). Nonsurvivors could be distinguished from survivors by an increase in NFkappaB binding activity during the observation period (P < 0.001). The increase in NFkappaB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IkappaBalpha was used to investigate the role of members of the NFkappaB family in a mouse model of endotoxemia. In this model, increased NFkappaB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IkappaBalpha given before LPS attenuated renal NFkappaB binding activity and increased survival. Endothelial cells and monocytes/macrophages were the major target cells for somatic gene transfer, transfected with an average transfection efficiency of 20-35%. Tissue factor, a gene under regulatory control of NFkappaB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFkappaB-dependent stimulation by LPS. Intravenous somatic gene transfer with IkappaBalpha reduced LPS-induced renal tissue factor expression, activation of the plasmatic coagulation system (decrease of thrombin-antithrombin III complexes) and renal fibrin/fibrinogen deposition. Somatic gene transfer with an expression plasmid with tissue factor cDNA in the antisense direction (in contrast to sense or vector alone) also increased survival. Furthermore, antisense tissue factor decreased renal tissue factor expression and the activation of the plasmatic coagulation system.

Version history
  • Version 1 (September 1, 1997): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts