dx-890 and fluorexon

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.. 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.. 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).. DX-890 reduces NE-mediated transmigration and inflammation. NE inhibition could be useful in managing neutrophilic airway inflammation in CF.

Topics: Anti-Inflammatory Agents; Cell Movement; Cells, Cultured; Cystic Fibrosis; Fluoresceins; Humans; In Vitro Techniques; Interleukin-8; Nasal Mucosa; Neutrophils; Peptides; Proteinase Inhibitory Proteins, Secretory