Journal article

Publication year: 2016

Pages: 325-331

Journal: Journal of Cystic Fibrosis

Volume number: 15

Issue number: 3

ISSN: 1569-1993

eISSN: 1873-5010

Open access status: Bronze

DOI Link: https://doi.org/10.1016/j.jcf.2015.10.008

Publisher: Elsevier

Abstract: 

Background: Neutrophil elastase (NE) rapidly degrades gel-forming airway mucins in cystic fibrosis (CF) sputum. We hypothesized that KRP-109, a small molecule NE inhibitor, would inhibit CF mucin degradation in vitro.

Methods: Sputa were collected from CF patients (n = 5) chronically or intermittently infected with Pseudomonas aeruginosa (P.a.). Mucin degradation was analyzed using western blot. Protease inhibitor studies were performed using alphal-proteinase inhibitor (A1-PI Prolastin (R)) and KRP-109. Elastase activity assays were performed using spectrophotometry.

Results: There were significant differences in the amount of active NE in different CF sputum samples. KRP-109 decreased the NE driven mucin degradation in vitro. Pseudomonas elastases appeared to blunt elastase inhibition by A1-PI or KRP-109.

Conclusion: Inhibitors of neutrophil and Pseudomonas-derived elastases might rescue mucus clearance and reverse airway obstruction in CF. (C) 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Harvard Citation style: Chillappagari, S., Mueller, C., Mahavadi, P., Guenther, A., Naehrlich, L., Rosenblum, J., et al. (2016) A small molecule neutrophil elastase inhibitor, KRP-109, inhibits cystic fibrosis mucin degradation, Journal of Cystic Fibrosis, 15(3), pp. 325-331. https://doi.org/10.1016/j.jcf.2015.10.008

APA Citation style: Chillappagari, S., Mueller, C., Mahavadi, P., Guenther, A., Naehrlich, L., Rosenblum, J., Rubin, B., & Henke, M. (2016). A small molecule neutrophil elastase inhibitor, KRP-109, inhibits cystic fibrosis mucin degradation. Journal of Cystic Fibrosis. 15(3), 325-331. https://doi.org/10.1016/j.jcf.2015.10.008