title: Anti-inflammatory effects of DX-890, a human neutrophil elastase inhibitor.
abstract: BACKGROUND
  Neutrophil elastase (NE)-mediated inflammation contributes to lung damage in cystic fibrosis (CF). We investigated if DX-890, a small-protein NE inhibitor, could reduce neutrophil trans-epithelial migration and reduce activity released from neutrophils and NE-induced cytokine expression in airway epithelial cells.
  
  
  METHODS
  Activated blood neutrophils (CF and healthy) treated ±DX-890 were assayed for NE activity. Transmigration of calcein-labeled neutrophils was studied using a 16HBE14o(-) epithelial monolayer. IL-8 release from primary nasal epithelial monolayers (CF and healthy) was measured after treatment ±DX-890 and NE or CF sputum.
  
  
  RESULTS
  DX-890 reduced NE activity from neutrophils (CF and healthy) and reduced neutrophil transmigration. DX-890 pre-treatment reduced IL-8 release from epithelial cells of healthy or CF subjects after stimulation with NE and CF sputum sol. All improvements with DX-890 were statistically significant (p<0.05).
  
  
  CONCLUSIONS
  DX-890 reduces NE-mediated transmigration and inflammation. NE inhibition could be useful in managing neutrophilic airway inflammation in CF.
authors.affiliation: Centre for Infection and Immunity, Queens University Belfast, Belfast BT9 7BL, UK.
authors.forename: Fiona K
authors.initials: FK
authors.lastname: Dunlevy
authors.forename: S Lorraine
authors.initials: SL
authors.lastname: Martin
authors.forename: Francine
authors.initials: F
authors.lastname: de Courcey
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
authors.forename: Madeleine
authors.initials: M
authors.lastname: Ennis
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000276:immunology*; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010455:Peptides / Q000494:pharmacology*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D005452:Fluoresceins; D016209:Interleukin-8; D010455:Peptides; D053491:Proteinase Inhibitory Proteins, Secretory; C512995:depelestat; C007740:fluorexon