Linked Life Data

17599828

Source:http://linkedlifedata.com/resource/pubmed/id/17599828

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-8-27
pubmed:abstractText
Mechanical ventilation can paradoxically cause acute lung injury, which is termed ventilator-induced lung injury. Neutrophil recruitment and neutrophil elastase release play a central role in the pathogenesis of ventilator-induced lung injury including cell damage, extracellular matrix degradation and alveolar-capillary hyperpermeability. We therefore speculated that neutrophil elastase inhibition ameliorates ventilator-induced lung injury. Anesthetized C57/BL6 mice received mechanical ventilation with a high tidal volume (V(T); 20 ml/kg) for 4 h. The neutrophil elastase inhibitor (sivelestat, 100 mg/kg) or saline was given intraperitoneally (i.p.) 30 min before ventilation. Sivelestat completely inhibited both neutrophil elastase and myeloperoxidase activities that were increased by ventilation, and attenuated the histopathological degree of lung damage, neutrophil accumulation and lung water content, as well as the concentration of macrophage inflammatory protein (MIP)-2, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid and serum. Moreover, mechanical ventilation increased the phosphorylation of c-Jun NH2-terminal kinase (JNK) and the expression of early growth response gene-1 (Egr-1) mRNA, and these increases were also recovered by sivelestat. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining revealed apoptotic cells mainly in alveolar epithelial cells and their numbers corresponded to histological damage. These data suggested that sivelestat could protect against ventilator-induced lung injury by suppressing apoptotic responses through mechanical stress-induced cell signaling in addition to inhibiting neutrophil chemotaxis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
571
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
62-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17599828-Animals, pubmed-meshheading:17599828-Apoptosis, pubmed-meshheading:17599828-Blotting, Western, pubmed-meshheading:17599828-Bronchoalveolar Lavage Fluid, pubmed-meshheading:17599828-Chemokine CXCL2, pubmed-meshheading:17599828-Chemokines, CXC, pubmed-meshheading:17599828-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:17599828-Glycine, pubmed-meshheading:17599828-Injections, Intraperitoneal, pubmed-meshheading:17599828-Interleukin-6, pubmed-meshheading:17599828-Leukocyte Elastase, pubmed-meshheading:17599828-Lung, pubmed-meshheading:17599828-Lung Diseases, pubmed-meshheading:17599828-Mice, pubmed-meshheading:17599828-Mice, Inbred C57BL, pubmed-meshheading:17599828-Mitogen-Activated Protein Kinases, pubmed-meshheading:17599828-Neutrophil Infiltration, pubmed-meshheading:17599828-Neutrophils, pubmed-meshheading:17599828-Pulmonary Edema, pubmed-meshheading:17599828-Serine Proteinase Inhibitors, pubmed-meshheading:17599828-Sulfonamides, pubmed-meshheading:17599828-Tumor Necrosis Factor-alpha, pubmed-meshheading:17599828-Ventilators, Mechanical
pubmed:year
2007
pubmed:articleTitle
Neutrophil elastase inhibitor (sivelestat) attenuates subsequent ventilator-induced lung injury in mice.
pubmed:affiliation
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan.
pubmed:publicationType
Journal Article