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Verfasst von:Brown, Ryan [VerfasserIn]   i
 Small, Donna M. [VerfasserIn]   i
 Doherty, Declan F. [VerfasserIn]   i
 Holsinger, Leslie [VerfasserIn]   i
 Booth, Robert [VerfasserIn]   i
 Williams, Richard [VerfasserIn]   i
 Ingram, Rebecca J. [VerfasserIn]   i
 Elborn, J. Stuart [VerfasserIn]   i
 Mall, Marcus A. [VerfasserIn]   i
 Taggart, Clifford C. [VerfasserIn]   i
 Weldon, Sinéad [VerfasserIn]   i
Titel:Therapeutic inhibition of cathepsin S reduces inflammation and mucus plugging in adult βENaC-Tg mice
Verf.angabe:Ryan Brown, Donna M. Small, Declan F. Doherty, Leslie Holsinger, Robert Booth, Richard Williams, Rebecca J. Ingram, J. Stuart Elborn, Marcus A. Mall, Clifford C. Taggart, and Sinéad Weldon
E-Jahr:2021
Jahr:20 Mar 2021
Umfang:10 S.
Teil:volume:2021
 year:2021
 elocationid:e6682657
 pages:1-10
 extent:10
Fussnoten:Gesehen am 02.06.2021
Titel Quelle:Enthalten in: Mediators of inflammation
Ort Quelle:Sylvania, Ohio : Hindawi Publishing Corp., 1992
Jahr Quelle:2021
Band/Heft Quelle:2021(2021), Artikel-ID e6682657, Seite 1-10
ISSN Quelle:1466-1861
Abstract:Background. Elevated levels of the cysteine protease cathepsin S (CatS) are associated with chronic mucoobstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). We have previously demonstrated that prophylactic treatment with a CatS inhibitor from birth reduces inflammation, mucus plugging, and lung tissue damage in juvenile β-epithelial Na+ channel-overexpressing transgenic (βENaC-Tg) mice with chronic inflammatory mucoobstructive lung disease. In this study, we build upon this work to examine the effects of therapeutic intervention with a CatS inhibitor in adult βENaC-Tg mice with established disease. Methods. βENaC-Tg mice and wild-type (WT) littermates were treated with a CatS inhibitor from 4 to 6 weeks of age, and CatS-/-βENaC-Tg mice were analysed at 6 weeks of age. Bronchoalveolar lavage (BAL) fluid inflammatory cell counts were quantified, and lung tissue destruction and mucus obstruction were analysed histologically. Results. At 6 weeks of age, βENaC-Tg mice developed significant airway inflammation, lung tissue damage, and mucus plugging when compared to WT mice. CatS-/-βENaC-Tg mice and βENaC-Tg mice receiving inhibitor had significantly reduced airway mononuclear and polymorphonuclear (PMN) cell counts as well as mucus plugging. However, in contrast to CatS-/-βENaC-Tg mice, therapeutic inhibition of CatS in βENaC-Tg mice had no effect on established emphysema-like lung tissue damage. Conclusions. These results suggest that while early CatS targeting may be required to prevent the onset and progression of lung tissue damage, therapeutic CatS targeting effectively inhibited airway inflammation and mucus obstruction. These results indicate the important role CatS may play in the pathogenesis and progression of mucoobstructive lung disease.
DOI:doi:10.1155/2021/6682657
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1155/2021/6682657
 Volltext: https://www.hindawi.com/journals/mi/2021/6682657/
 DOI: https://doi.org/10.1155/2021/6682657
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1759427039
Verknüpfungen:→ Zeitschrift

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