• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1999 Fiscal Year Final Research Report Summary

Basic Studies of Novel Gene Therapy by Regulation of Transcription of the Inflammation-Related Gene.

Research Project

Project/Area Number 10670436
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionInstitute of Medical Science, St.Marianna University

Principal Investigator

KAWAI Shinichi  Institute of Medical Science, St.Marianna University School of Medicine, 難病治療研究センター, 教授 (70129401)

Co-Investigator(Kenkyū-buntansha) MAEKAWA Kohtaroh  Hisamitsu Pharmaceutical Co., 筑波研究所, 研究員
Project Period (FY) 1998 – 1999
Keywordsantisense DNA / new carrier / IL-1β / TNF-α / synovial cells / rheumatoid arthritis / Ki-ras gene / Tripterygium wilfordii Hook F
Research Abstract

To investigate novel anti-inflammatory therapies, we studied a novel carrier for antisense DNA, targeted to pro-inflammatory cytokines. We developed poly-L-lysine/L-serine-polyethylene glycol (PLSP) as a carrier for antisense DNA. Our previous study (Antisense Nucl Acid Drug Dev 6:55-61, 1996) showed that antisense phosphorothioate oligonucleotide targeted to the initiation codon of human interliukin-1β(Il-1β) suppressed production of IL-1β of U937 cells. Then, we used the antisense DNA of IL-1β to examine the effects of several kinds of PLSP. 10kDa and 15kDa molecules of the PSLP were the most potent among them. However, a considerable toxicity and instability were observed when the PSLP was used. We further examined the effects of antisense phosphorothioate oligonucleotide targeted to some sequences of human tumor necrosis factor (TNF)-α gene. In this case, no positive effect was observed. We then studied the anti-inflammatory effects of Tripterygium wilfordii Hook F extract (GTW). GTW inhibited prostaglandin EィイD22ィエD2 production in the human synovial cells due to suppression of cyclooxgenase-2 protein and mRNA, which is similar to those of glucocorticoid. However, the mechanism of action of the GTW was different from that of glucocorticoid. It inhibited nuclear factor-ィイD2KィエD2B activity without acting on glucocorticoid receptor. We also examined effects of changes in signal transduction by introduction of Ki-ras gene into human synovial cells from patients with rheumatoid arthritis. Stimulation by cytokines including TNF-α reduced proliferation rate of ras-introduced synovial cells, whereas they enhanced proliferation on nontreated synovial cells. The mechanism remains to be studied.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Yamazaki R, Kawai S, et al.: "Hydrolytic activity is essential for aceclofenac to inhibit cyclooxygenase in rheumatoid synovial cells"J Pharmacol Exp Ther. 289(0). 676-681 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Asanuma Y, Kawai S, et al.: "Serum lipoprotein(a) and apolipoprotein(a) phenotypes in patients with rheumatoid arthritis"Arthritis Rheum. 42(3). 443-447 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawai S, et al.: "18 years mitotane therapy for intractable Cushing's disease"Lancet. 354(9182). 951 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Asanuma Y, Kawai S: "Lipoprotein(a) levels and atherosclerosis in rheumatoid arthritis ; Author's reply"Arthritis Rheum. 42(11). 2491-2492 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maekawa K, Kawai S, et al.: "The molecular mechanism of inhibition of interleukin-1 β-induced cyclooxygenase-2 expression in human synovial cells by Tripterygium wilfordii Hook F extract"Inflamm Res. 48(11). 575-581 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawai S: "Cushing's disease ; Author's reply"Lancet. 355(9197). 68 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitasaato H, Okamoto R, Kawai S: "Arthritis Rheum"Absence of p53 mutation in Japanese patients with rheumatoid arthritis. 469-470 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamazaki R, Kawai S, et al.: "Inflamm Res"A major metabolite of aceclofenac, 4'-hydroxy aceclofenac, suppresses the production of interstitial pro-collagenase/proMMP-1 and pro-stromelysin-1/proMMP-3 by human rheumatoid synovial cells.

    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2001-10-23  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi