Feng Qiu
Dr. sc. hum
Rolle von Mitgliedern der NF-κB, bZIP Familie und Tissue Factor bei der Endotoxin-
vermitteltern Lethalität
Geboren am 27.04.1963 in HangZhou, V R China
Reifeprüfung am 01.08.1981 in HangZhou
Studiengang der Fachrichtung Biochemie vom SS 1981 bis WS 1985
Vordiplom am 01.09.1985 an der Universität: Amoy Universität, Xiamen, V R China
Diplom am 01.09.1990an der Universität: CNRRI, HangZhou, V R China
Promotionsfach: Innere Medizin
Doktorvater: Priv.-Doz Dr. med. P. P. Nawroth
The patient study and the animal study complement each other in demonstrating that
endotoxin mediated activation of the transcription factors NF-κB and AP-1 play a central role
in vivo. The transcription factors nuclear factor κB (NF-κB) and activator protein-1 (AP1) are
believed to control genes, which play an important role in the pathogenesis of sepsis. The NF-
κB and AP1 binding activities were determined in nuclear extracts of monocytes isolated
from 15 patients with sepsis (10 survivors, and 5 non-survivors). Non-survivors could be
distinguished from survivors by an increase in NF-κB (p<0.001) and AP1 (p<0.05) binding
activities. The increase in NF-κB and AP1 binding activities was a stronger predictor of
outcome than the APACHE II score. Intravenous somatic gene transfer with an expression
plasmid coding for IκBα or mutated Jun (a form of Jun capable of binding Fos, but not DNA)
was used to investigate the role of members of the NF-κB and the basic-leucine zipper protein
(bZIP) families in an animal model of sepsis. Intravenous somatic gene transfer with IκBα
and m-Jun increased survival, decreased renal NF-κB and AP1 binding activities, decreased
tissue factor expression, reduced the activation in the plasmatic coagulation system. 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, decreased tissue factor
expression and also reduced the activation of the plasmatic coagulation system. Somatic gene
transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated
NF-κB and AP1-dependent stimulation by endotoxin in vivo. Thus, members of the NF-κB
and bZIP families play an important role in endotoxin-mediated sepsis, partly due to
regulation of tissue factor transcription.
