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Chillappagari, S.* ; Müller, C.* ; Mahavadi, P.* ; Guenther, A.* ; Nahrlich, L.* ; Rosenblum, J.* ; Rubin, B.K.* ; Henke, M.O.

A small molecule neutrophil elastase inhibitor, KRP-109, inhibits cystic fibrosis mucin degradation.

J. Cyst. Fibros. 15, 325-331 (2016)
Verlagsversion Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 alpha1-proteinase inhibitor (A1-PI Prolastin®) 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cystic Fibrosis ; Mucin ; Protease And Anti-protease Balance ; Small Molecule Inhibitors; Lung-disease; Pseudomonas-aeruginosa; Alpha-1-proteinase Inhibitor; Iron Homeostasis; Proteases; Inflammation; Efficacy; Alpha(1)-antitrypsin; Safety; Antiproteases
Sprache englisch
Veröffentlichungsjahr 2016
Prepublished im Jahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1569-1993
e-ISSN 1873-5010
Zeitschrift Journal of Cystic Fibrosis
Quellenangaben Band: 15, Heft: 3, Seiten: 325-331 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Lung Research
PSP-Element(e) G-505000-007
DOI 10.1016/j.jcf.2015.10.008
WOS ID WOS:000377728800010
Scopus ID 84969549257
PubMed ID 26526358
Erfassungsdatum 2015-11-05
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