Cathepsin C inhibition reduces neutrophil serine protease activity and improves activated neutrophil-mediated disorders

Yuka Nishibata, Suishin Arai, Mai Taniguchi, Issei Nakade, Hodaka Ogawa, Shota Kitano, Yumeka Hosoi, Ayano Shindo, Ryo Nishiyama, Sakiko Masuda, Daigo Nakazawa, Utano Tomaru, Takafumi Shimizu, William Sinko, Tadashi Nagakura, Yoh Terada and Akihiro Ishizu ()
Additional contact information
Yuka Nishibata: Hokkaido University
Suishin Arai: Hokkaido University
Mai Taniguchi: Hokkaido University
Issei Nakade: Hokkaido University
Hodaka Ogawa: Hokkaido University
Shota Kitano: Hokkaido University
Yumeka Hosoi: Hokkaido University
Ayano Shindo: Hokkaido University
Ryo Nishiyama: Hokkaido University
Sakiko Masuda: Hokkaido University
Daigo Nakazawa: Hokkaido University
Utano Tomaru: Hokkaido University Hospital
Takafumi Shimizu: Inc.
William Sinko: Inc.
Tadashi Nagakura: Inc.
Yoh Terada: Inc.
Akihiro Ishizu: Hokkaido University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Cathepsin C (CatC) is an enzyme which regulates the maturation of neutrophil serine proteases (NSPs) essential for neutrophil activation. Activated neutrophils are key players in the innate immune system, and are also implicated in the etiology of various inflammatory diseases. This study aims to demonstrate a therapeutic potential for CatC inhibitors against disorders in which activated neutrophil-derived neutrophil extracellular traps (NETs) play a significant role. We demonstrate that a CatC inhibitor, MOD06051, dose-dependently suppresses the cellular activity of NSPs, including neutrophil elastase (NE), in vitro. Neutrophils derived from MOD06051-administered rats exhibit significantly lower NE activity and NET-forming ability than controls. Furthermore, MOD06051 dose-dependently ameliorates vasculitis and significantly decreases NETs when administered to a rat model of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody-associated vasculitis (AAV). These findings suggest that CatC inhibition is a promising strategy to reduce neutrophil activation and improve activated neutrophil-mediated diseases such as MPO-AAV.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50747-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50747-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50747-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().