Arthritogenic action of gliostatin in rheumatoid arthritis and its molecular mechanism
| Project/Area Number |
14571392
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Nagoya City University |
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Principal Investigator |
NAGAYA Yuko Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究科, 助手 (90291583)
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| Co-Investigator(Kenkyū-buntansha) |
ASAI Kiyohumi Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (70212462)
OTSUKA Takanobu Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (10185316)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | gliostatin / rheumatoid arthritis / synovitis / steroid / aurothioglucose / synoviocytes / Interleukin-1 beta / interleukin-1β |
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| Research Abstract |
Neovascularization, proliferation of synovial cells, and mononuclear cell influx and activation are characteristic events observed in synovial joints in the pathohistology of rheumatoid arthritis (RA). We have previously measured the concentration of the angiogenic factor, gliostatin (GLS), in sera and synovial fluids of RA patients, and demonstrated for the first time an enormously high concentration in RA synovial fluids as well as in RA sera. Furthermore our previous study demonstrated that GLS acts as a cytokine to augment its own synthesis in fibroblast-like synoviocytes (FLSs) obtained from patients with RA through an autocrine mechanism. It should be noted that GLS additionally caused induction and extracellular secretion of matrix metalloproteinase (MMP)-1 and MMP-3 triggering cartilage degeneration. Recently we reported that intraarticular injection of rHuGLS to rabbit knees induced RA-like synovitis. The purpose of this study was to investigate whether disease modified antirheumatic drugs (DMARDs) is involved in the regulation of GLS expression.
FLSs were cultured and stimulated interleukin (IL)-1beta with or without DMARDs. Expression levels of GLS were determined by reverse transcription-polymerase chain reaction methods and enzyme-linked immunosorbent assays. In cultured rheumatoid FLSs GLSmRNA were found to be markedly increased by stimulation of IL-1beta. GLSmRNA in IL-1beta-stimulated FLSs were reduced by aurothioglucose and dexamethasone in a dose dependent manner. Methotrexate and sulfasalazine had no major influence on GLS production.
These findings indicate that aurothioglucose and dexamethasone are responsible for the anti-rheumatic activity mediated via inhibition GLS production.
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Report
(3 results)
Research Products
(12 results)
