title: Neutrophil elastase ameliorates matrix metalloproteinase-9 to promote lipopolysaccharide-induced acute lung injury in mice 1.
abstract: OBJECTIVE
  To investigate the regulatory roles of neutrophil elastase (NE) and matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.
  
  
  METHODS
  To construct LPS-induced ALI mouse models, wild-type C57BL/6 mice were administered 5.0 mg/kg of LPS through endotracheal, and/or 1.0 mg/kg of ONO-5046, and/or 20.0 mg/kg of chemically modified tetracycline-3 (CMT-3) by gavage. The levels of MMP-9, tissue inhibitor of metalloprotease-1, interleukin (IL)-6 were detected by real time RT-PCR at 6 h, 24 h and 48 h, and tumor necrosis factor (TNF), lung wet-dry weight ratio, white blood cell (WBC) count and polymorphonuclear (PMN) count in bronchoalveolar lavage fluid (BALF) were tested at 48 h after administration. The 5-day survival analysis of the ALI mice was also performed.
  
  
  RESULTS
  Both ONO-5046 and CMT-3, regardless of being used individually or combined, significantly reduced the levels of MMP-9, IL-6, and TNF in lung tissue as well as in BALF, and the WBC and PMN count in BALF. Combined treatment with ONO-5046 and CMT-3 remarkably improved the survival rate of ALI mice.
  
  
  CONCLUSIONS
  Neutrophil elastase synergizes with matrix metalloproteinase-9 to promote and regulate the release of inflammatory mediators and the infiltration of inflammatory cells, consequently affecting the survival of lipopolysaccharide-induced acute lung injury mice.
authors.affiliation: Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved.|Department of Emergency or Respiration, First Affiliated, General Hospital of PLA, Beijing, China. Statistical analysis, technical procedures, final approved the manuscript.
authors.forename: Yingfei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved.|Department of Emergency or Respiration, First Affiliated, General Hospital of PLA, Beijing, China. Statistical analysis, technical procedures, final approved the manuscript.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved.
authors.forename: Rongju
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Emergency, General Hospital of PLA, Beijing, China. Design the protocol, acquisition and analysis of data, technical procedures, manuscript writing, final approved.
authors.forename: Tanshi
authors.initials: T
authors.lastname: Li
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009504:Neutrophils; D013449:Sulfonamides / Q000008:administration & dosage*; D016019:Survival Analysis; D013754:Tetracyclines / Q000008:administration & dosage*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013449:Sulfonamides; D013754:Tetracyclines; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D048069:Tumor Necrosis Factors; C577686:interleukin-6, mouse; C117155:tetracycline CMT-3; C069195:sivelestat; D019272:Leukocyte Elastase; D020780:Matrix Metalloproteinase 9; D005998:Glycine