Anti-inflammatory effects of DX-890, a human neutrophil elastase inhibitor

Fiona K. Dunlevy, S. Lorraine Martin, Francine de Courcey, J. Stuart Elborn, Madeleine Ennis

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)300-304
Number of pages4
JournalJournal of Cystic Fibrosis
Volume11
Issue number4
Early online date12 Mar 2012
DOIs
Publication statusPublished - Jul 2012

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pediatrics, Perinatology, and Child Health

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