[The effect of transmembrane- and secreted-tumor necrosis factor-alpha on shock liver].
OBJECTIVE
To observe the dynamic expression of transmembrane (TM)-tumor necrosis factor (TNF)-alpha and secreted (S)-TNF-alpha in the development of endotoxic shock and explore the actions and mechanism of TM-TNF-alpha in liver of the rat with endotoxic shock.


METHODS
Endotoxic shock in rats was induced by intravenous injection of dead gram negative bacteria E. Coli; the kinetics of TM-TNF-alpha on peritoneal macrophages and S-TNF-alpha in serum of these rats were determined. Pretreatment with TNF alpha converting enzyme antisense oligonucleotide (5 mg/kg) 30 minutes before rats were administrated dead bacteria inhibited enzymatic cleavage of TM-TNF-alpha into S-TNF-alpha. Six hours after bacteria injection, TM-TNF-alpha and S-TNF-alpha were also detected respectively. The pathological injury in the livers of rats with endotoxin shock was examined, and artery pressure was constantly measured.


RESULTS
The kinetics of TM-TNF-alpha expression in the development of endotoxic shock was different from that of S-TNF-alpha expression in serum. The expression of TM-TNF-alpha began to increase on the surface of peritoneal macrophages and liver within 30 min, after bacteria challenge and peaking within a period of 4.5 hours followed by a gradual decrease to a relatively high level which was maintained for at least 24 hours. The TACE antisense oligonucleotide pretreated rats showed remarkable increase in TM-TNF-alpha expression by peritoneal macrophages and liver (P < 0.001), and their arterial blood pressure were maintained within normal levels and there were no detectable pathological changes in their livers.


CONCLUSIONS
These findings suggested that TM-TNF-alpha may be a potent endogenous regulator involved in anti-inflammatory responses to maintain normal arterial pressure and protect liver tissue from pathological injury in during endotoxin shock. This study confirmed the important role of TNF-alpha in endotoxic shock which is not only of important theoretical significance, but also of practical interest in providing experimental basis for clinical treatment of endotoxin shock.
Yin
Bingjiao
B
Institute of Immunology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. ybjzm79@hotmail.com
Li
Zhuoya
Z
Yu
Shangbin
S
Jiang
Xiaodan
X
Feng
Wei
W
Xu
Yong
Y
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D008107:Liver Diseases / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004731:Endotoxins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha