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タイトル: | Nardilysin is involved in autoimmune arthritis via the regulation of tumour necrosis factor alpha secretion |
著者: | Fujii, Takayuki Nishi, Eiichiro Ito, Hiromu Yoshitomi, Hiroyuki https://orcid.org/0000-0001-7339-9030 (unconfirmed) Furu, Moritoshi Okabe, Namiko Ohno, Mikiko Nishi, Kiyoto Morita, Yusuke Morita, Yugo Azukizawa, Masayuki Okahata, Akinori Tomizawa, Takuya Kimura, Takeshi Matsuda, Shuichi |
著者名の別形: | 藤井, 貴之 西, 英一郎 伊藤, 宣 |
発行日: | 1-Jul-2017 |
出版者: | BMJ |
誌名: | RMD Open |
巻: | 3 |
号: | 1 |
論文番号: | e000436 |
抄録: | Objective: Tumour necrosis factor alpha (TNF-α) plays an important role in rheumatoid arthritis (RA). TNF-α is synthesised as a membrane-anchored precursor and is fully activated by a disintegrin and metalloproteinase 17 (ADAM17)-mediated ectodomain shedding. Nardilysin (NRDC) facilitates ectodomain shedding via activation of ADAM17. This study was undertaken to elucidate the role of NRDC in RA. Methods: NRDC-deficient (Nrdc–/– ) mice and macrophage-specific NRDC-deficient (NrdcdelM ) mice were examined in murine RA models, collagen antibody-induced arthritis (CAIA) and K/BxN serum transfer arthritis (K/BxN STA). We evaluated the effect of gene deletion or silencing of Nrdc on ectodomain shedding of TNF-α in macrophages or monocytes. NRDC concentration in synovial fluid from patients with RA and osteoarthritis (OA) were measured. We also examined whether local gene silencing of Nrdc ameliorated CAIA. Results: CAIA and K/BxN STA were significantly attenuated in Nrdc–/– mice and NrdcdelM mice. Gene deletion or silencing of Nrdc in macrophages or THP-1 cells resulted in the reduction of TNF-α shedding. The level of NRDC is higher in synovial fluid from RA patients compared with that from OA patients. Intra-articular injection of anti-Nrdcsmall interfering RNA ameliorated CAIA. Conclusion: These data indicate that NRDC plays crucial roles in the pathogenesis of autoimmune arthritis and could be a new therapeutic target for RA treatment. |
記述: | 新たな関節リウマチ治療のターゲット分子としてのナルディライジン. 京都大学プレスリリース. 2017-07-11. |
著作権等: | © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
URI: | http://hdl.handle.net/2433/226418 |
DOI(出版社版): | 10.1136/rmdopen-2017-000436 |
PubMed ID: | 28955486 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2017-07-11 |
出現コレクション: | 学術雑誌掲載論文等 |
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