| Project/Area Number |
16590987
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Nagasaki University |
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Principal Investigator |
KAWAKAMI Atsushi Nagasaki University, Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (90325639)
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| Co-Investigator(Kenkyū-buntansha) |
ORIGUCHI Tomoki Nagasaki University, Graduate School of Biomedical Sciences, associate professor, 大学院・医歯薬学総合研究科, 助教授 (90295105)
IDA Hiroaki Nagasaki University, Hospital of Medicine and Dentistry, assistant, 医学部・歯学部附属病院, 助手 (60363496)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | fibroblast-like synovial cells / rheumatoid arthritis (RA) / cytokine / IFN-γ / cellular differentiation / JAK / STAT / TRAIL-mediated apoptosis / apoptosis-related molecule / 滑膜線維芽細胞(FLS) / アポトーシス / Akt / P13-K / CaMKII / FLS / 分化 / TRAIL依存性アポトーシス / 蛋白合成 / caspase-8 |
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| Research Abstract |
Hyperplasia of fibroblast-like synovial cells is a characteristic feature in patients with rheumatoid arthritis (RA). Inflammatory cytokines as well as growth factors, expressed in situ of rheumatoid synovial tissues, are suggested to induce "apoptosis-resistant phenotype" of fibroblast-like synovial cells. In addition, these humoral factors may involve in the differentiation process of fibroblast-like synovial cells ; a newly denoted function of the cells. We have examined how cytokines modulate the process of both apoptosis sensitivity and cellular differentiation. As for the effect of IFN-γ toward fibroblast-like synovial cells, IFN-γ significantly suppressed the expression of PPAR-γ and C/EBP nuclear activity, and thus inhibited PPAR-γ ligand-induced adipocyte-like cell differentiation from fibroblast-like synovial cells. Furthermore, IFN-γ treatment markedly phosphorylated STAT proteins through JAK, leading to induce "apoptosis-resistant phenotype" toward TRAIL. Our data suggest that IFN-γ induces the two phenomena ; "inhibition of cellular differentiation" and "induction of apoptosis-resistant phenotype" through distinct signaling cascades, however, further studies, including the elucidation of signal cross-talks of kinase cascades in the above two phenomena, should be necessary to approach the molecular mechanism.
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