title: [TNFR-Fc prevents lipopolysaccharide-induced acute lung injury in mice via oxidative stress inhibition].
abstract: OBJECTIVE
  Acute lung injury (ALI) was associated with excessive inflammation caused by high TNF-α concentration. We hypothesized that anti-TNF-α therapy would have beneficial effects in experimental ALI in mice via oxidative stress inhibition.
  
  
  METHODS
  BALB/c mice (8 - 10 week old) were randomly assigned to an LPS group, a TNFR-Fc + LPS group and a control group. LPS (5 mg/kg) was intratracheally administered to the mice. For the TNFR-Fc + LPS group, TNFR-Fc was given intraperitoneally once at a dose of 0.4 mg/kg before LPS treatment, at 0 and 2 h after LPS treatment, the mice were sacrificed. Wet to dry ratio of the lung and the protein concentration in BALF were measured. Lung histology was evaluated for lung injury. TNF-α concentration in serum, MDA and total anti-oxidative stability were assayed. Finally, the transcription level of iNOS, Nox1, Nox2, Nox4, XO and SOD were evaluated by qRT-PCR.
  
  
  RESULTS
  TNFR-Fc treatment significantly decreased the serum TNF-α concentration (P < 0.001), reduced the score of lung histology and decreased the protein concentration in BALF (P < 0.001), but did not change the wet to dry ratio of the lung. The ALI mice treated with TNFR-Fc had a lower transcription level of Nox1, Nox2, Nox4 and XO (all P < 0.001). The total anti-oxidative stability of mice treated with TNFR-Fc was preserved better than those treated with LPS alone (P < 0.05).
  
  
  CONCLUSIONS
  Treatment with TNFR-Fc significantly reduced LPS-induced ALI. The transcription level of Nox and XO was down-regulated by anti-TNF-α therapy, followed by oxidative stress attenuation.
authors.affiliation: Department of Respiratory Medicine, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Wei-feng
authors.initials: WF
authors.lastname: Yuan
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Wei-feng
authors.initials: WF
authors.lastname: Li
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000068800:Etanercept; D005260:Female; D007074:Immunoglobulin G / Q000494:pharmacology*; D007249:Inflammation; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept