2002 年度実績報告書

ステロイド依存性リンパ球アポトーシスの分子機序と疾患病態における意義に関する研究

研究課題

研究課題/領域番号	13470047
研究機関	北海道大学
研究代表者	上出利光北海道大学, 遺伝子病制御研究所, 教授 (00160185)
研究分担者	今重之北海道大学, 遺伝子病制御研究所, 助手 (90344499)
キーワード	胸腺細胞 / アポトーシス / 遺伝子導入マウス / ステロイド / カスペース
研究概要	1.グルココルチコイド(GC)刺激による胸腺細疱のアポトーシスに先行して、発現誘導されるDIG-1遺伝子を未熟Tリンパ球に強制発現させたトランスジェニックマウス(TG)を作成した。 2.上記TGマウスでは、胸腺細胞分化に影響が認められた。すなちCD8陽性びCD4陰性CD8陰性胸腺細胞(DN)の増加が認められた。DN細胞の中でCD25^<mid>CD44^<high>の分画が特に増加していた。 3.ステロイドによりアポトーシスを示す胸腺細胞数は増加したが、放射線及びTCR刺激によるアポトーシスは増加しなかった。DIG-1遺伝子はステロイドによるアポトーシスに特異性の高い事が証明された。 4.TGをステロイドで刺激すると、対照群に比して著明にカスペース3,8,9の活性上昇が認められた。DIG-1の下流にカスペースが存在することが示唆された。 5.TGと対象群のマウスにステロイドを投与し、胸腺細胞における遺伝子発現プロファイリングをDNAチップを用いて検討した。TGでは対照群に比較して、c-MybとDok-2の発現が著名に減少していた。これはDIG-1によるアポトーシス経路の下流にc-MybとDok-2が存在する事を示唆する所見である。 6.TGではc-Mybが減少することによりbcl-2の発現が減少し、このためにステロイードによるアポトーシスが亢進すると考えられた。

研究成果
(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Kanaya, K.: "Combined gene therapy with adenovirus vectors containing CTLA4Ig and CD40Ig prolongs survival of composite tissue allografts in ratmodel"Transplantation.. 75. 275-281 (2003)
[文献書誌] Koguchi, Y.: "High plasma osteopontin level and its relationship with IL-12-mediated Th1 response in tuberculosis"Am J Respir Crit Care Med.. 5. (2003)
[文献書誌] Nagamori, N.: "Intrinsic and extrinsic manipulation of B7/CTLA-4 interaction for induction of anti-tumor immunity against osteosarcoma cells"Anticancer Res.. 22. 3223-3227 (2002)
[文献書誌] Ohshima, S.: "Enhanced local production of osteopontin in rheumatoid joints"J Rheumatol.. 29. 2061-2067 (2002)
[文献書誌] Tsuji, H.: "Adenovirus-mediated in vivo B7-1 gene transfer induces anti-tumor immunity against pre-established primary tumor and pulmonary metastasis of rat osteosarcoma"Cancer Gene Ther. 9. 745-755 (2002)
[文献書誌] Nagamori, N.: "In vivo immunogenicity of osteosarcoma cells that express B7-1a, an alternatively spliced form of B7-1"Anticancer Res.. 22. 2009-2103 (2002)
[文献書誌] Kimura, F.: "Locally expressed CTLA4-Ig in a pancreatic beta-cell line suppresses acceleratedgraft rejection response induced by donor-specific transfusion"Diabetologia.. 45. 831-840 (2002)
[文献書誌] Shiraishi, T.: "Prevention of acute lung allograft rejection in rat by CTLA4Ig"Am J Transplant.. 2. 223-228 (2002)
[文献書誌] Konishi, K.: "Combination treatment with FTY72O and CTLA4IgG preserves the respiratory epithelium and prevents obliterative disease in a murine airway model"J Heart Lung Transplant.. 21. 692-700 (2002)
[文献書誌] Chiba, S.: "Development of atherosclerosis in osteopontin transgenic mice"Heart Vessels.. 16. 111-117 (2002)
[文献書誌] Nomura, M.: "Induction of donor-specific tolerance by adenovirus-mediated CD40Ig gene therapy in rat liver transplantation"Transplantation. 15. 1403-1410 (2002)
[文献書誌] Ohshima, S.: "Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen-induced arthritis : possible involvement of osteopontin in bone destruction in arthritis"Arthritis Rheum.. 46. 1094-1101 (2002)
[文献書誌] Matsui, Y.: "Blockade of T cell costimulatory signals using adenovirus vectors prevents both the induction and the progression of experimental autoimmune myocarditis"J Moll Cell Cardiol.. 34. 279-295 (2002)
[文献書誌] Yumoto, K.: "Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice"Proc Natl Acad Sci U S A.. 99. 4556-4561 (2002)
[文献書誌] Kim, JH.: "Osteopontin as a potential diagnostic biomarker for ovarian cancer"JAMA.. 287. 1671-1679 (2002)
[文献書誌] Iwasaki, N.: "Feasibility of immunosuppression in composite tissue allografts bysystemic administration of CTLA4Ig"Transplantation.. 73. 334-340 (2002)
[文献書誌] Koguchi, Y.: "Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells"Infect Immun.. 70. 1042-1048 (2002)
[文献書誌] Kon, S.: "Mapping of functional epitopes of osteopontin by monoclonal antibodies raised against defined internal sequences"J Cell Biochem. 84. 420-432 (2002)

2002 年度 実績報告書

ステロイド依存性リンパ球アポトーシスの分子機序と疾患病態における意義に関する研究

研究代表者

上出 利光 北海道大学, 遺伝子病制御研究所, 教授 (00160185)

研究成果

[文献書誌] Kanaya, K.: "Combined gene therapy with adenovirus vectors containing CTLA4Ig and CD40Ig prolongs survival of composite tissue allografts in ratmodel"Transplantation.. 75. 275-281 (2003)

[文献書誌] Koguchi, Y.: "High plasma osteopontin level and its relationship with IL-12-mediated Th1 response in tuberculosis"Am J Respir Crit Care Med.. 5. (2003)

[文献書誌] Nagamori, N.: "Intrinsic and extrinsic manipulation of B7/CTLA-4 interaction for induction of anti-tumor immunity against osteosarcoma cells"Anticancer Res.. 22. 3223-3227 (2002)

[文献書誌] Ohshima, S.: "Enhanced local production of osteopontin in rheumatoid joints"J Rheumatol.. 29. 2061-2067 (2002)

[文献書誌] Tsuji, H.: "Adenovirus-mediated in vivo B7-1 gene transfer induces anti-tumor immunity against pre-established primary tumor and pulmonary metastasis of rat osteosarcoma"Cancer Gene Ther. 9. 745-755 (2002)

[文献書誌] Nagamori, N.: "In vivo immunogenicity of osteosarcoma cells that express B7-1a, an alternatively spliced form of B7-1"Anticancer Res.. 22. 2009-2103 (2002)

[文献書誌] Kimura, F.: "Locally expressed CTLA4-Ig in a pancreatic beta-cell line suppresses acceleratedgraft rejection response induced by donor-specific transfusion"Diabetologia.. 45. 831-840 (2002)

[文献書誌] Shiraishi, T.: "Prevention of acute lung allograft rejection in rat by CTLA4Ig"Am J Transplant.. 2. 223-228 (2002)

[文献書誌] Konishi, K.: "Combination treatment with FTY72O and CTLA4IgG preserves the respiratory epithelium and prevents obliterative disease in a murine airway model"J Heart Lung Transplant.. 21. 692-700 (2002)

[文献書誌] Chiba, S.: "Development of atherosclerosis in osteopontin transgenic mice"Heart Vessels.. 16. 111-117 (2002)

[文献書誌] Nomura, M.: "Induction of donor-specific tolerance by adenovirus-mediated CD40Ig gene therapy in rat liver transplantation"Transplantation. 15. 1403-1410 (2002)

[文献書誌] Ohshima, S.: "Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen-induced arthritis : possible involvement of osteopontin in bone destruction in arthritis"Arthritis Rheum.. 46. 1094-1101 (2002)

[文献書誌] Matsui, Y.: "Blockade of T cell costimulatory signals using adenovirus vectors prevents both the induction and the progression of experimental autoimmune myocarditis"J Moll Cell Cardiol.. 34. 279-295 (2002)

[文献書誌] Yumoto, K.: "Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice"Proc Natl Acad Sci U S A.. 99. 4556-4561 (2002)

[文献書誌] Kim, JH.: "Osteopontin as a potential diagnostic biomarker for ovarian cancer"JAMA.. 287. 1671-1679 (2002)

[文献書誌] Iwasaki, N.: "Feasibility of immunosuppression in composite tissue allografts bysystemic administration of CTLA4Ig"Transplantation.. 73. 334-340 (2002)

[文献書誌] Koguchi, Y.: "Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells"Infect Immun.. 70. 1042-1048 (2002)

[文献書誌] Kon, S.: "Mapping of functional epitopes of osteopontin by monoclonal antibodies raised against defined internal sequences"J Cell Biochem. 84. 420-432 (2002)

2002 年度実績報告書

上出利光北海道大学, 遺伝子病制御研究所, 教授 (00160185)