2001 Fiscal Year Final Research Report Summary
The pathophysiological significance of proteases in patients with chronic inflammatory joint disease
| Project/Area Number |
12671421
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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 | The University of Tokushima |
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Principal Investigator |
NAKANO Shunji The University of Tokushima, School of Medicine, Research Associate, 医学部・附属病院, 助手 (60294683)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHARA Shigeyuki The University of Tokushima, University Hospital, Clinical Fellow, 医学部・附属病院, 医員(臨床)
TAKEDA Yoshitugu The University of Tokushima, University Hospital, Lecturer, 医学部・附属病院, 講師(前分担者) (20243694)
YASUOKA Susumu The University of Tokushima, School of Medical Science, Professor, 医療技術短期大学部, 教授(前分担者) (30035414)
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| Project Period (FY) |
2000 – 2001
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| Keywords | proteas / rheumatoid arthritis / osthoarthritis / synovial fluid / synovium |
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| Research Abstract |
To clarify the pathophysiological significance of proteases in RA and OA, we investigated what kinds of proteases were specifically activated in both synovial fluid and synovial tissue of RA ＆ OA patients , and effects of serine proteases on release of inflammatory cytokines from synovial cells.
We obtained the following fmdings. (I) When the protease substrates were incubated with SF supernatants, thrombin was the most preferentially hydrolyzed while trypsin substrate and cathepsin B substrate were hydrolyzed to some degree. In the case of SF cell extracts, cathepsin B substrate was the most preferentially hydrolyzed while the other substrates were hardly hydrolyzed. In the case of synovial tissue extracts, cathepsin B substrate was the most preferentially hydrolyzed while trypsin substrate was hydrolyzed to some degree. Protease activities were in general significantly higher in RA than in OA. (II) Thrombin (0.1 to 100 units /ml) significantly enhanced growth of the synovial fibroblast-like cells (FC). When SFC were cultured with thrombin (100 units/ml) or MCT (10 ng/ml), concentrations of IL-8 and IL-6 in the culture medium were significantly increased compared with the control, while the concentrations of IL-1□, IL-1□ and TNF-□ were not detectable in all the culture mediums. (III) Cathepsin B-like protease purified from both the SF and synovial tissues ofRA patients was mainly composed of cathepsin B, and the cathepsin B purified from SF samples ofRA patients was capable of activating prourokinase to urokinase in vitro.
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