Research of antibody therapy and gene therapy targeting to chemokine and its receptor
| Project/Area Number |
20591525
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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 |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
UENO Takehisa Osaka University, 医学系研究科, 助教 (10456957)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUZAWA Masahiro 大阪大学, 医学系研究科, 教授 (60165272)
MIYAGAWA Shuji 大阪大学, 医学系研究科, 准教授 (90273648)
TAKAMA YUICHI 大阪大学, 医学部附属病院, 医員 (50467560)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 小腸移植 / 虚血再還流 / 急性拒絶 / ケモカイ / ELISA / フローサイトメトリー / TECK,Fractalkine / TECK, Fractalkine / ケモカイン / TECK / Fractalkine |
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| Research Abstract |
The effects of FK506, and TAK-779, antagonists of CCR5 and CXCR3, were investigated using a rat intestinal transplantation model. Small intestines from DA rats were heterotopically transplanted into LEW rats. The recipients were treated with FK506 (1mg/kg/day, day 0-5) and TAK-779 (10mg/kg/day, day 0-10). Graft survival and immunological responses to these materials were estimated by mixed lymphocyte reactions and IFN-_ production. The expression of chemokine receptors on lymphocytes was also examined. The average duration of survival was 7.0±0.3, 12.0±1.0, 9.8±0.5 and 18.0±1.5 days in the allogeneic, FK506, TAK-779 and the two-drug combined groups, respectively. Cell proliferative responses and IFN-_ production were suppressed to a significant extent in the FK506 group compared with the TAK-779 group. In addition, the two-drug combination showed a tendency for stronger suppression than FK506 alone, correlated with in vivo and histopathological data. The numbers of both CD4+ and CD8+ cells were significantly suppressed in the blood of the recipients of both the FK506 and the TAK-779 groups, and in Peyer's patches of the graft of the TAK-779 group, but the FK506 group was not, as evidenced by FACS analysis. In addition, double-staining of graft-infiltrating lymphocytes showed a significant reduction in lymphocyte numbers, expressing CCR5 and CXCR3 in the TAK-779 group, but not evident in the FK506 group, compared to the allogeneic group. While FK506 suppresses cell proliferation and effecter function, it has less effect on the expression of CCR5 and CXCR3 in lymphocytes. Further exploration of the effects of a combined therapy with TAK-779 could represent a novel treatment for intestinal transplantation
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Effects of a calcineurin inhibitor, FK506, and a CCR5/CXCR3 antagonist,TAK-779, in a rat small intestinal transplantation model2011
Author(s)
Yuichi Takama, Shuji Miyagawa, Aki Yamamoto, Sabere Firdawes, TakehisaUeno, Yoshiyuki Ihara, Akihiro Kondo, Katsuyoshi Matsunami, Hideaki Otsuka, Masahiro Fukuzawa
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Journal Title
Transplant Immunology Epub ahead of print
Related Report
Peer Reviewed
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