| Project/Area Number |
17591028
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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 | University of Tsukuba |
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Principal Investigator |
TSUTSUMI Akito University of Tsukuba, Graduate School of Comprehensive Human Science, Associate Professor, 大学院人間総合科学研究科, 助教授 (60250453)
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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 |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | rheumatoid arthritis / tumor necrosis factor a / posttranscriptional regulation / tristetraprolin / biologics / TNFα / 一塩基多型 / AU-rich element / HuR / TIA-1 |
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| Research Abstract |
Tristetraproline (TTP) is an intracellular protein that destabilizes TNFa.mRNA and suppresses TNF α production. We aimed to analyze the role of TTP in rheumatoid arthritis (RA)
1. Introduction of the TTP gene into a Human T cell line resulted in reduction of the TNFα mRNA. Response to PHA stimulation was also decreased.
2. No significant relationship was observed between the expressions of TTP, TIA-1 or HuR gene, and serum CRP in synovial tissues from patients with RA. However, significant relationship between. gene expressions of TIA-1 and HuR was found.
3. Gene expressions of TNFa, TIA-1, TIA-1/HuR were higher and TTP, HuR, TTP/TNFa, TTP/HuR lower in peripheral blood mononuclear cells (PBMC) of RA patients than those from controls. TTP/HuR decreased after introduction of Infliximab. Significant relationships were observed between expression of TIA-1 and TNFα, and TTP and TIA-1 in controls and RA patients after Infliximab treatment. TIA-1/HuR before Infliximab therapy tended to be higher in Infliximab effective patients.
4. RA patients with genotype GG of a SNP in the promoter region of the TTP gene tended to have an earlier age of onset than those with AG or AA.They also had a higher probability of having Infliximab introduced.
5. TTP transgenic mice tended to be more resistant to collagen induced arthritis than controls.
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