論文

査読有り
2009年6月

Intervention of an Inflammation Amplifier, Triggering Receptor Expressed on Myeloid Cells 1, for Treatment of Autoimmune Arthritis

ARTHRITIS AND RHEUMATISM
  • Yousuke Murakami
  • ,
  • Tohru Akahoshi
  • ,
  • Naoko Aoki
  • ,
  • Masayasu Toyomoto
  • ,
  • Nobuyuki Miyasaka
  • ,
  • Hitoshi Kohsaka

60
6
開始ページ
1615
終了ページ
1623
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/art.24554
出版者・発行元
WILEY-LISS

Objective. Triggering receptor expressed on myeloid cells 1. (TREM-1.) is inducible on monocyte/macrophages and neutrophils and accelerates tissue destruction by propagating inflammatory responses in disease related to bacterial infections. Its blockade rescues the hosts in murine models of sepsis, to clear the bacteria without impairing the host defense. The aim of this study was to investigate the involvement of TREM-1. in an autoimmune, noninfectious disease.
Methods. Synovial tissue specimens from the joints of patients with rheumatoid arthritis (RA) and the joints of mice with collagen-induced arthritis (CIA) were examined for TREM-1 expression, using flow cytometric analysis. Expression of TREM-1 on macrophages was induced by lipopolysaccharide, with or without a cyclooxygenase inhibitor. Rheumatoid synovial cells were stimulated with agonistic anti-TREM-1 antibodies. Recombinant adenovirus encoding the extracellular domain of TREM-1. fused with IgG-Fc (AxCATREM-1 Ig) or synthetic TREM-1. antagonistic peptides were injected to treat CIA, and the clinical manifestations of the antigen-specific T cell and B cell responses were evaluated.
Results. TREM-1 was expressed on CD14+ cells in rheumatoid synovial tissue and synovial macrophages from mice with CIA. Unlike murine macrophages, human monocyte/macrophages did not depend on prostaglandin E(2) for up-regulation of TREM-1. Agonistic anti-TREM-1 antibodies promoted tumor necrosis factor a production from rheumatoid synovial cells. Blockade of TREM-1 using AxCATREM-1 Ig and antagonistic peptides ameliorated CIA without affecting the serum levels of anti-type II collagen antibodies or the proliferative responses of splenocytes to type II collagen.
Conclusion. TREM-1 ligation contributes to the pathology of autoimmune arthritis. The results of this study implied that blockade of TREM-1 could be a new approach to rheumatic diseases that is safer than the presently available immunosuppressive treatments.

Web of Science ® 被引用回数 : 53

リンク情報
DOI
https://doi.org/10.1002/art.24554
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000267116800009&DestApp=WOS_CPL
ID情報
  • DOI : 10.1002/art.24554
  • ISSN : 0004-3591
  • Web of Science ID : WOS:000267116800009

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