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

Nishibata, Yuka; Arai, Suishin; Taniguchi, Mai; Nakade, Issei; Ogawa, Hodaka; Kitano, Shota; Hosoi, Yumeka; Shindo, Ayano; Nishiyama, Ryo; Masuda, Sakiko; Nakazawa, Daigo; Tomaru, Utano; Shimizu, Takafumi; Sinko, William; Nagakura, Tadashi; Terada, Yoh; Ishizu, Akihiro

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

Nishibata, Yuka; Arai, Suishin; Taniguchi, Mai et al.

Nature Communications, 2024, 15(1), 6519

Permalink : https://hdl.handle.net/2115/92985

このアイテムのアクセス数:198件（2026-08-08 15:15 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
https://doi.org/10.1038/s41467-024-50747-6			13

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/92985
タイトル	Cathepsin C inhibition reduces neutrophil serine protease activity and improves activated neutrophil-mediated disorders
著者	Nishibata, Yuka ; Arai, Suishin ; Taniguchi, Mai ; Nakade, Issei ; Ogawa, Hodaka ; Kitano, Shota ; Hosoi, Yumeka ; Shindo, Ayano ; Nishiyama, Ryo ; Masuda, Sakiko ; Nakazawa, Daigo ; Tomaru, Utano ; Shimizu, Takafumi ; Sinko, William ; Nagakura, Tadashi ; Terada, Yoh ; Ishizu, Akihiro
e-Rad_Researcher 90899791 著者名 Nishibata, Yuka
著者名 Arai, Suishin
著者名 Taniguchi, Mai
著者名 Nakade, Issei
著者名 Ogawa, Hodaka
著者名 Kitano, Shota
著者名 Hosoi, Yumeka
著者名 Shindo, Ayano
著者名 Nishiyama, Ryo
e-Rad_Researcher 10763617 著者名 Masuda, Sakiko
著者名 Nakazawa, Daigo
著者名 Tomaru, Utano
著者名 Shimizu, Takafumi
著者名 Sinko, William
著者名 Nagakura, Tadashi
著者名 Terada, Yoh
e-Rad_Researcher 60321957 著者名 Ishizu, Akihiro
言語	英語
キーワード	Immunohistochemistry
	Neutrophils
	Vasculitis syndromes
発行日	2024-08-22
出版者	Springer Nature
収録物名	Nature Communications
巻(号)	15(1)
ページ	6519
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
EISSN	2041-1723
NCID	AA12645905
関連情報	PMID 39174512
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1038/s41467-024-50747-6