Pathogenic role of newly identified regulatory molecule in autoimmune arthritis
Project/Area Number |
21591261
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
膠原病・アレルギー・感染症内科学
|
Research Institution | University of Tsukuba |
Principal Investigator |
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | リウマチ学 / 関節リウマチ / TNFa / TIARP / シトルリン化蛋白 / GPI / 自己抗体 / ACPA / glucose-6-phosphate isomerase / TNFα / STEAP4 |
Research Abstract |
1)TIARP-/-mice developed spontaneous arthritis, had high serum levels of IL-6, increased CD11b+ cell count in the spleen, and showed enhanced TNF-induced IL-6 expression in macrophages. Sustained degradation of IkBa with dysregulated apoptosis was also noted in TIARP-/-macrophages, and they showed increased IL-6-induced STAT3 phosphorylation. These findings suggested that TIARP is a negative regulator in arthritis by suppressing IL-6 production, its signaling and TNFa-induced NF-kB signaling result in enhanced apoptosis in macrophages. 2)Nine cyclic citrullinated GPI peptides (CCG-1-9) were constructed. Samples were obtained from patients with RA (n=208), healthy subjects (n=174) and other autoimmune diseases (n=202). Anti-CCG-2, 4, 7 Abs were detected in about 30.0% patients with RA, and these Abs were very specific of RA (specificity 99%). Anti-CCG-2, 4, 7 Abs were correlated with anti-CCP, CEP-1 and the presence of HLA-DRB1 SE allele. Treatment with TNF antagonists significantly reduced the levels of anti-CCG-2, 7, suggesting possible diagnostic and activity marker of RA.
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Report
(4 results)
Research Products
(73 results)
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[Book] 日本臨床免疫学会雑誌2010
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