title: [The effect of transmembrane- and secreted-tumor necrosis factor-alpha on shock liver].
abstract: 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.
authors.affiliation: Institute of Immunology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. ybjzm79@hotmail.com
authors.forename: Bingjiao
authors.initials: B
authors.lastname: Yin
authors.forename: Zhuoya
authors.initials: Z
authors.lastname: Li
authors.forename: Shangbin
authors.initials: S
authors.lastname: Yu
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: 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*
chemical_list: D004731:Endotoxins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha