| Project/Area Number |
17591572
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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 | Kobe University |
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Principal Investigator |
MIURA Yasushi Kobe University, School of Medicine, Associate Professor, 医学部, 助教授 (60346244)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIRAMOTO Akira Kobe University, School of Medicine, Honorary Associate Professor, 医学部, 客員助教授 (80346246)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Rheumatoid Arthritis / Apoptosis / TL1A / DR3 |
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| Research Abstract |
Prior to the model arthritis experiment using with TL1A knock out mice, we investigated the functions of decoy receptor 3 (DcR3), a newly identified soluble receptor binding to TL1A. DcR3 is mostly expressed in tumor cells and competitively inhibits TNF binding to TNFR. We investigated DcR3 expression in rheumatoid fibroblast-like synovial cells (RA-FLS) and osteoarthritis fibroblast-like synovial cells (OA-FLS), and analyzed the functions of DcR3 to Fas-induced apoptosis in RA-FLS. Methods : Expression of DcR3 in FLS was measured by RT-PCR and Western blotting. FLS were incubated with DcR3-Fc chimera protein or transfected with DcR3 siRNA using the lipofection method before induction of apoptosis. Results: (1) DcR3 was expressed in both RA-FLS and OA-FLS.(2)The expression levels of DcR3 mRNA were not significantly different between RA and OA. (3) Pre-treatment with recombinant DcR3-Fc protein inhibited Fas-induced apoptosis in FLS in a dose dependent manner. (4) Downregulation of DcR3 by siRNA increased Fas-induced apoptosis in both RA-FLS and OA-FLS. (5) TNF-alpha increased DcR3 expression and inhibited Fas-induced apoptosis in RA-FLS, but not in OA-FLS. Conclusion: DcR3 expressed in RA-FLS is increased by TNF-alpha and protects the cells from Fas-induced apoptosis.
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