| Project/Area Number |
19590741
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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 |
Gastroenterology
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| Research Institution | Kurume University |
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Principal Investigator |
MITSUYAMA Keichi Kurume University, 医学部, 准教授 (20200066)
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| Co-Investigator(Kenkyū-buntansha) |
TSURUTA Osamu 久留米大学, 医学部, 教授 (60197770)
KUWAKI Kotaro 久留米大学, 医学部, 助教 (60425171)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 炎症性腸疾患 / colitic cancer / IL-6 trans-signaling / STAT3 / 可溶性gp130-Fc / 可溶性gp 130-Fc / 可溶性gp130 |
|---|
| Research Abstract |
Colitic cancer is a large bowel cancer that occurs in a long-standing inflammatory bowel disease. The role of the IL-6/STAT3 pathway in the development of colitic cancer has not been fully understood. This study was conducted to investigate whether IL-6 trans-signaling contributes to the development of colitic cancer. Chronic colitis was induced by dextran sodium sulfate (DSS) to BALB/c mice. Colitic cancer was induced by additional DSS treatment to colitis-affected mice. IL-6 expression increased in the colon of colitis- and colitic cancer-affected mice, and this expression was restricted to lamina propria-macrophages. Both IL-6R and TACE expressions increased in macrophages in colitis tissue, and soluble IL6R was increased in these tissues. In contrast, IL-6R generation was reduced in the colonic epithelial cells in colitis- and colitic cancer-mice and was associated with increased expression of gp130 and phospho-STAT3. It should be noted that pre-treatment of soluble gp130Fc significantly reduced the tumorigenesis in the colon. IL-6 trans-signaling in epithelial cells, induced by macrophage-derived IL-6/soluble IL-6R, plays a crucial role in the development of colitic cancer. Soluble gp130Fc may be effective for the prevention of colitic cancer.
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