Development of new therapeutic modalities for Rheumatoid Arthritis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Juntendo University (2013-2014); The University of Tokyo (2012)
• Principal Investigator: IWATA SATOSHI 順天堂大学, 医学(系)研究科(研究院), 講師 (00396871)
• Co-Investigator(Renkei-kenkyūsha): MORIMOTO Chikao 順天堂大学, 大学院医学研究科, 教授 (30119028)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 関節リウマチ / コラーゲン誘導関節炎 / 接着分子 / インテグリン / ドッキング蛋白質 / Cas-L / Nedd9 / マクロライド

Outline of Final Research Achievements

Cas-L is a cytoplasmic docking protein essential for cellular migration and beta 1 integrin-mediated costimulation of T cells. Our current study expanded these findings on the role of Cas-L in the development of rheumatoid arthritis (RA) by analyzing the pathophysiological changes in a Cas-L -/- mouse collagen-induced arthritis (CIA) model, strongly suggesting that Cas-L plays a pivotal role in the pathophysiology of CIA, and that Cas-L may be a potential molecular target for the treatment of RA.
Macrolide antibiotics have immunomodulatory properties that are distinct from their anti-bacterial functions. We synthesized 5-I, which is a new derivative of roxithromycin with less antimicrobial activity, and evaluated its immunomodulatory effects. Administration of 5-I to mice with CIA reduced the severity of arthritis, and this effect was also observed when treatment was delayed till after the onset of disease, suggesting that 5-I may be useful as a potential therapeutic agent for RA.

Free Research Field

リウマチ学