|Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
In the mutated TGF-β1 knock-in mouse which mutated latent type TGF-β1 and made combination impossible with LTBP in order that we might analyze the mechanism of the latent type TGF-β1 activation in vive, It turned out that the symptoms of pneumonia, a cardiac muscle inflamation, and colitis are shown from after 4 weeks old, and inflammation becomes chronic in after 8 to 12 week of age.
It found out that spontaneous stomach cancer, rectal cancer, and anal cancer, after inflammation becomes chronic was observed. Furthermore, by the gene expression analysis of colorectum with colitis, the expression of IL-l(3, TNF-a, IL-6 and IFN-y were elevated, and that of IL-17 was decreased.
The immunohistochemical analysis showed the increase of IL-6 expression in colorectal epithelium, and elevated signals of phosphorylation STATs and Ki67 in nucleus. It is indicated that cytokine expression of IL-6 etc. mediated in the colorectal epithelium may induce the hyperplasia in colorectal epithelium through a
ctivation of STAT3.
Moreover, in the analysis of the colorectal mucosal lymphocyte, Foxps positive T lymphocyte and an IL-li positive T lymphocyte and the increase in an IFN-y positive T lymphocyte were observed. In colorectal epithelium, it was suggested that Thl was dominant and that the population of Trea and Thli are decreased.
In the analysis of integrin 138 knockout and a mutated TUFF-fsl knock-in mouse, it turned out that the incidence of stomach, rectal and colon cancer was 60. 0% 16. 7% and 66. 7%, respectively(under paper preparation).
We got preliminary data which showed that mating with Rag2 knockout mouse and a mutated TGF-lsl knock-in mouse, it turned out that the incidence of carcinoma was decreased. Under the environment of low activation of TGF-lsl, lack of the cytospecific immunity which is mediated by DC contributes to carcinogenesis in gastrointesitinal tract, however, in the situation without the cell immunity itself, it is conversely difficult to mediate carcinogenesis in gastrointesitinal tract. Less