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

作者：Dunlevy Fiona K; Martin S Lorraine; de Courcey Francine; Elborn J Stuart; Ennis Madeleine^*

来源：Journal of Cystic Fibrosis, 2012, 11(4): 300-304.

DOI：10.1016/j.jcf.2012.02.003

• Cystic fibrosis
• Epithelial
• Protease
• Airway

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. %26lt;br%26gt;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. %26lt;br%26gt;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%26lt;0.05). %26lt;br%26gt;Conclusions: DX-890 reduces NE-mediated transmigration and inflammation. NE inhibition could be useful in managing neutrophilic airway inflammation in CF.

• 出版日期2012-7