2004 Fiscal Year Final Research Report Summary
GENE-EXPRESSION PROFILES OF THE PERIPHERAL BLOOD MONONUCLEAR CELLS FROM TOLERANT RAT AND LIVING-DONOR LIVER TRANSPLANT RECIPIENTS
| Project/Area Number |
14370367
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | National Research Institute for Child Health and Development |
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Principal Investigator |
LI X-k. Natl.Res.Inst.For Child Health. & Dev., Dept.of Innovative Surgery, Lab Head, 移植・外科研究部, 室長 (60321890)
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| Co-Investigator(Kenkyū-buntansha) |
FUNESHINA N. Natl.Res.Inst.For Child Health. & Dev., Dept.of Surgical Research, Researcher, 共同研究管理室, 流動研究員 (60399483)
UEMOTO S. Mie University School of Medicine, Dept.of Surgery, Professor, 医学部・第一外科講座, 教授 (40252449)
鈴木 英年 浜松医科大学, 第一外科講座, 研究生
FUJINO M. Natl.Inst.of Infectious Disease, AIDS Res.Ctr, Researcher, エイズ研究センター・第二研究グループ, 研究員 (50392329)
SUZUKI H. Hamamatus University School of Medicine, Dept.of Surgery, Asst.Professor
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| Project Period (FY) |
2002 – 2004
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| Keywords | transplantation immunology / tolerance / regulatory cell / gene / co-stimulatory / DNA chip |
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| Research Abstract |
Induction of transplant tolerance to allogeneic donor grafts is a clinically desirable goal, and ongoing research underscores the need for new scientific inquiry. In an effort to provide unbiased insight into transplant tolerance, we took an approach involving gene expression profiling in peripheral blood mononuclear cells from Tacrolimus (FK506) induced tolerance of the fully mismatched liver allograft rat and the recipients of living-donor liver transplants(LDLT) who had retained an immune tolerance with a well-functioning graft for several years. First, we compared mRNA profiles in PBL from tolerant recipients with those from syngeneic recipients using a DNA microarray with probe sets corresponding to more than 8000 rat genes. There were 96 up-regulated and 103 down-regulated genes in the tolerant recipients. In the up-regulated group, there were 76 known genes and 20 expressed sequence tags(ESTs). In the down-regulated groups, there were 87 known genes and 16 ESTs. Our data indicat
… More
ed that FK506 treatment induced tolerance and expansion of regulatory cells and the DNA microarray technology was useful for this application and provided many informative insights into the mechanism of lymphocyte regulation. Second, employing comparative analyses with non-transplanted normal healthy volunteers, we demonstrated that the majority of reliable detected genes were similar, implying a steady state between the two groups and allowing us to define a set of tolerant signature genes. We determined that 5.6% of the genes in the tested genome (of which 627 up-regulated and 90 down-regulated) were significantly regulated and specific to tolerant LDLT recipients, indicating a significant genetic feature for inducing and maintaining immune tolerance. Notably, both gene-related immune response and cell membrane were shown to have distinct transcript categorized profiles. Moreover, the expression of several selected genes was confirmed by semi-quantitative RT-PCR, which correlated to microarray data. Our data indicated that cDNA microarray technology was useful for this application and provided many informative insights into transplant tolerance mechanisms. Less
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[Journal Article] The enhanced effects of biodegradable microsphere loaded tacrolimus on mice islet allograft and its reduced adverse effects on insulin secretion.2004
Author(s)
QX Wang, T.Uno, Y.Miyamoto, Y.Hara, Y.Kitazawa, FZ Lu, N.Funeshima, M.Fujino, H.Yamamoto, H.Takenaka, Y.Kawashima, X-K.Li.
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Journal Title
Am J Transplant 4(5)
Pages: 721-727
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] AdCTLA-4Ig combined with donor splenocytes, bone marrow cells and anti-ICOS antibody treatment result in a distinct tolerant state in rat heart transplantation model2004
Author(s)
L Guo, M.Fujino, H.Kimura, N.Funeshima, Y.Kitazawa, Y.Harihara, K.Tezuka, M.Makuuchi, S.Suzuki, X-K.Li.
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Journal Title
Transpl Int 17(1)
Pages: 15-21
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Successful in utero gene transfer using a gene gun in midgestational mouse fetuses.2004
Author(s)
J.Yoshizawa J, X-K.Li, M.Fujino, H.Kimura, R.Mizuno, A.Hara, S.Ashizuka, M.Kanai, N.Kuwashima, M.Kurobe, Y.Yamazaki
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Journal Title
J Pediatr Surg. 39(1)
Pages: 81-84
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Simultaneous Blockade of Co-stimulatory Signals, CD28 and ICOS, Induced a Stable Tolerance in Rat Heart Transplantation.2003
Author(s)
L Guo, M.Fujino, H.Kimura, N.Funeshima, Y.Kitazawa, Y.Harihara, K.Tezuka, M.Makuuchi, S.Suzuki, X-K.Li
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Journal Title
Transpl Immunol 12(1)
Pages: 41-48
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] CrmA gene expression protects mice against concanavalin-A induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis.2003
Author(s)
M.Fujino, M.Kawasaki, N.Funeshima, Y.Kitazawa, M.Kosuga, K.Okabe, M.Hashimoto, H.Yaginuma, K.Mikoshiba, T.Okuyama, S.Suzuki, X-K.Li
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Journal Title
Gene Ther 10(20)
Pages: 1781-1790
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prolongation of transgene by co-expression of cytokine response modifier A in rodent liver after adenoviral gene transfer.2002
Author(s)
X-K.Li, M.Kosuga, K.Tokieda, A.Kanaji, Y.Fukuhara, M.Hashimoto, K.Okabe, H.Yaginuma, M.Yamada, S.Suzuki, T.Okuyama
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Journal Title
Mol Ther 5
Pages: 262-268
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prolonged survival in rat liver transplantation woth mouse monoclonal antibody against an inducible co-stimulator(ICOS).2002
Author(s)
L Guo, X-K.Li, N.Funeshima, M.Fujino, Y.Nagata, H.Kimura, H.Amemiya, S.Enosawa, T.Tsuji, Y.Harihara, M.Makuuchi, S.Suzuki
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Journal Title
Transplantation 73(7)
Pages: 1027-1032
Description
「研究成果報告書概要(欧文)」より
