The role of TL1A in inflammatory bowel disease
| Project/Area Number |
21790690
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 炎症性腸疾患 / TL1A / death receptor 3 / Death receptor 3 |
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| Research Abstract |
The pathogenicrole of TL1A in inflammatory bowel disease has been shown in several studies. In this study, we evaluated the role of TL1A in acute colitis and the association between TL1A and Th2.
We showed that TL1A expression from macrophages and DR3 expression from intestinal epithelial cells was increased in DSS-colitis mice. In human intestinal epithelial cell lines, DR3 expression was increased by the stimulation of IL-1 and IL-6. Indeed, DR3 expression was increased in intestinal epithelial cells from Crohn's Disease patients compared with normal and ulcerative colitis. These results suggested that the interaction of TL1A and DR3 on intestinal epithelial cells was important to develop acute colitis. Then, we performed the treatment of neutralizing anti-TL1A antibodies in DSS acute colitis. Anti-TL1A treatment attenuated acute colitis, however there was not a significant difference of body weight, colon length, and cytokine expression between control group and treatment group. We made siRNA of TL1A because we could not have an enough amount of anti-TL1A antibodies. We are going to continue to study the treatment of siRNA in DSS acute colitis.
Furthermore, we investigated whether TL1A activated Th2 cells. In our study, SAMP1/Yit mice which spontaneously develop severe ileitis, were used. TL1A was significantly increased in ileum of SAMP1/Yit mice. Mononuclear cells isolated from mesenteric lymph nodes were stimulated with TL1A, IL-12, IL-23, IL-13 and their combinations. In this experiment, we showed that TL1A activated not only Th1and Th17, but also Th2 cells.
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Report
(3 results)
Research Products
(7 results)
