Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Neutrophil elastase inhibitor (sivelestat) attenuates subsequent ventilator-induced lung injury in mice. 1759 28