2017年7月1日
Nardilysin is involved in autoimmune arthritis via the regulation of tumour necrosis factor alpha secretion
RMD Open
- 巻
- 3
- 号
- 1
- 開始ページ
- e000436
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1136/rmdopen-2017-000436
- 出版者・発行元
- BMJ Publishing Group
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.
- リンク情報
-
- DOI
- https://doi.org/10.1136/rmdopen-2017-000436
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/28955486
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604610
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85024396094&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85024396094&origin=inward
- ID情報
-
- DOI : 10.1136/rmdopen-2017-000436
- ISSN : 2056-5933
- eISSN : 2056-5933
- PubMed ID : 28955486
- PubMed Central 記事ID : PMC5604610
- SCOPUS ID : 85024396094