Role of NFκB in the mortality of sepsis

Hubert Böhrer, Feng Qiu, Thomas Zimmermann, Youming Zhang, Thomas Jllmer, Daniela Männel, Bernd W. Böttiger, David Stern, Rüdiger Waldherr, Hans Detlev Saeger, Reinhard Ziegler, Angelika Bierhaus, Eike Martin, Peter P. Nawroth

Research output: Contribution to journalArticle

422 Citations (Scopus)

Abstract

Binding activity for nuclear factor kappa B (NFκB) 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 NFκB binding activity during the observation period (P < 0.001). The increase in NFκB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IκBα was used to investigate the role of members of the NFκB family in a mouse model of endotoxemia. In this model, increased NFκB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IκBα given before LPS attenuated renal NFκB 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 NFκB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFκB-dependent stimulation by LPS. Intravenous somatic gene transfer with IκBα 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.

Original languageEnglish (US)
Pages (from-to)972-985
Number of pages14
JournalJournal of Clinical Investigation
Volume100
Issue number5
DOIs
StatePublished - Sep 1 1997

Fingerprint

NF-kappa B
Sepsis
Thromboplastin
Mortality
Genes
Kidney
Plasmids
APACHE
Endotoxemia
Survival
Regulator Genes
Fibrin
Fibrinogen
Transfection
Survivors
Monocytes
Blood Cells
Endothelial Cells
Complementary DNA
Macrophages

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Böhrer, H., Qiu, F., Zimmermann, T., Zhang, Y., Jllmer, T., Männel, D., ... Nawroth, P. P. (1997). Role of NFκB in the mortality of sepsis. Journal of Clinical Investigation, 100(5), 972-985. https://doi.org/10.1172/JCI119648

Role of NFκB in the mortality of sepsis. / Böhrer, Hubert; Qiu, Feng; Zimmermann, Thomas; Zhang, Youming; Jllmer, Thomas; Männel, Daniela; Böttiger, Bernd W.; Stern, David; Waldherr, Rüdiger; Saeger, Hans Detlev; Ziegler, Reinhard; Bierhaus, Angelika; Martin, Eike; Nawroth, Peter P.

In: Journal of Clinical Investigation, Vol. 100, No. 5, 01.09.1997, p. 972-985.

Research output: Contribution to journalArticle

Böhrer, H, Qiu, F, Zimmermann, T, Zhang, Y, Jllmer, T, Männel, D, Böttiger, BW, Stern, D, Waldherr, R, Saeger, HD, Ziegler, R, Bierhaus, A, Martin, E & Nawroth, PP 1997, 'Role of NFκB in the mortality of sepsis', Journal of Clinical Investigation, vol. 100, no. 5, pp. 972-985. https://doi.org/10.1172/JCI119648
Böhrer H, Qiu F, Zimmermann T, Zhang Y, Jllmer T, Männel D et al. Role of NFκB in the mortality of sepsis. Journal of Clinical Investigation. 1997 Sep 1;100(5):972-985. https://doi.org/10.1172/JCI119648
Böhrer, Hubert ; Qiu, Feng ; Zimmermann, Thomas ; Zhang, Youming ; Jllmer, Thomas ; Männel, Daniela ; Böttiger, Bernd W. ; Stern, David ; Waldherr, Rüdiger ; Saeger, Hans Detlev ; Ziegler, Reinhard ; Bierhaus, Angelika ; Martin, Eike ; Nawroth, Peter P. / Role of NFκB in the mortality of sepsis. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 5. pp. 972-985.
@article{ad8058c3bd1946fc867a02eeebd6132f,
title = "Role of NFκB in the mortality of sepsis",
abstract = "Binding activity for nuclear factor kappa B (NFκB) 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 NFκB binding activity during the observation period (P < 0.001). The increase in NFκB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IκBα was used to investigate the role of members of the NFκB family in a mouse model of endotoxemia. In this model, increased NFκB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IκBα given before LPS attenuated renal NFκB 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 NFκB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFκB-dependent stimulation by LPS. Intravenous somatic gene transfer with IκBα 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.",
author = "Hubert B{\"o}hrer and Feng Qiu and Thomas Zimmermann and Youming Zhang and Thomas Jllmer and Daniela M{\"a}nnel and B{\"o}ttiger, {Bernd W.} and David Stern and R{\"u}diger Waldherr and Saeger, {Hans Detlev} and Reinhard Ziegler and Angelika Bierhaus and Eike Martin and Nawroth, {Peter P.}",
year = "1997",
month = "9",
day = "1",
doi = "10.1172/JCI119648",
language = "English (US)",
volume = "100",
pages = "972--985",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

TY - JOUR

T1 - Role of NFκB in the mortality of sepsis

AU - Böhrer, Hubert

AU - Qiu, Feng

AU - Zimmermann, Thomas

AU - Zhang, Youming

AU - Jllmer, Thomas

AU - Männel, Daniela

AU - Böttiger, Bernd W.

AU - Stern, David

AU - Waldherr, Rüdiger

AU - Saeger, Hans Detlev

AU - Ziegler, Reinhard

AU - Bierhaus, Angelika

AU - Martin, Eike

AU - Nawroth, Peter P.

PY - 1997/9/1

Y1 - 1997/9/1

N2 - Binding activity for nuclear factor kappa B (NFκB) 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 NFκB binding activity during the observation period (P < 0.001). The increase in NFκB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IκBα was used to investigate the role of members of the NFκB family in a mouse model of endotoxemia. In this model, increased NFκB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IκBα given before LPS attenuated renal NFκB 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 NFκB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFκB-dependent stimulation by LPS. Intravenous somatic gene transfer with IκBα 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.

AB - Binding activity for nuclear factor kappa B (NFκB) 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 NFκB binding activity during the observation period (P < 0.001). The increase in NFκB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IκBα was used to investigate the role of members of the NFκB family in a mouse model of endotoxemia. In this model, increased NFκB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IκBα given before LPS attenuated renal NFκB 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 NFκB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFκB-dependent stimulation by LPS. Intravenous somatic gene transfer with IκBα 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.

UR - http://www.scopus.com/inward/record.url?scp=0030611086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030611086&partnerID=8YFLogxK

U2 - 10.1172/JCI119648

DO - 10.1172/JCI119648

M3 - Article

C2 - 9276714

AN - SCOPUS:0030611086

VL - 100

SP - 972

EP - 985

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 5

ER -