Molecular analysis of steroid-induced apoptosis and its relevance to disease pathogenesis.

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 13470047
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: UEDE Toshimitsu Hokkaido Univ., Inst. For Genetic Med., Prof., 遺伝子病制御研究所, 教授 (00160185)
• Co-Investigator(Kenkyū-buntansha): KON Shigeyuki Hokkaido Univ., Inst. For Genetic Med., Inst., 遺伝子病制御研究所, 助手 (90344499)
• Project Period (FY): 2001 – 2003
• Keywords: Thymocyte / Apoptosis / Transgenic mice / steroid / caspase

Research Abstract

1. Trangenic mice (TG) was established in which TDAG8 gene responsible for glucocorticoid-induced apoptosis was over-expressed.
2. The expression of mRNA including FasL, FADD, TRAIL, TNF-R and TRADD did not differ between TG and control mice upon glucocorticoid treatment.
3. TG mice exhibited augmented thymocyte apoptosis induced by glucocorticoid as compared to control mice.
4. Upon glucocorticoid treatment, activity of caspase 3, 8, and 9 was significantly augmented in TG mice as compared to control mice.

Research Products

• [Publications] Morimoto, J.: "Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms."Int Immunol.. 16・3. 477-488 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ishii, T.: "Mice with osteopontin deletion remain predisposed to collagen-induced arthritis."Arthritis Rheum.. 50・2. 669-671 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tanaka, K.: "Effect of osteopontin alleles on beta-glucan-induced granuloma formation in the mouse liver."Am J Pathol.. 164・2. 567-575 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ono, E.: "Resistance to pseudorabies virus infection in transformed cell lines expressing a soluble form of porcine herpesvirus entry mediator C."J Gen Virol.. 85・1. 173-178 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamashita, K.: "Long-term acceptance of rat cardiac allografts on the basis of adenovirus mediated CD40Ig plus CTLA4Ig gene therapies."Transplantation.. 76・7. 1089-1096 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Saeki, Y.: "Enhanced production of osteopontin in multiple myeloma : clinical and pathogenic implications."Br J Haematol.. 123・2. 263-270 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Maeda, K., Takahashi, K., Takahashi, F., Tamura, N., Maeda, M., Kon, S., Uede, T., Fukuchi, Y.: "Distinct roles of osteopontin fragments in the development of the pulmonary involvement in sarcoidosis."Lung. 179(5). 279-291 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Weiss, JM., Renkl, AC., Maier, CS., Kimmig, M., Liaw, L., Ahrens, T., Kon, S., Maeda, M., Hotta, H., Uede, T., Simon, JC.: "Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes."J Exp Med. 194(9). 1219-1229 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ijima, K., Murakami, M., Okamoto, H., Inobe, M., Chikuma, S., Saito, I., Kanegae, Y., Kawaguchi, Y., Kitabatake, A., Uede T.: "Successful gene therapy via intraarticular injection of adenovirus vector containing CTLA4IgG in a marine model of type II collagen-induced arthritis."Hum Gene Ther. 12(9). 1063-1077 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takahashi, F., Takahashi, K., Okazaki, T., Maeda, K., Ienaga, H., Maeda, M., Kon, S., Uede, T., Fukuchi, Y.: "Role of osteopontin in the pathogenesis of bleomycin-induced pulmonary fibrosis."Am J Respir Cell Mol Biol. 24(3). 264-271 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takehara, M., Murakami, M., Inobe, M., Tanaka, K., Chikuma, S., Saito, I., Kanegae, Y., Yasunami, Y., Nakano, M., Yamashita, K., Todo, S., Uede, T.: "Long-term acceptance of allografts by in vivo gene transfer of regulatable adenovirus vector containing CTLA4IgG and loxP."Hum Gene Ther. 12(4). 415-426 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iwabuchi, K., Iwabuchi, C., Tone, S., Itoh, D., Tosa, N., Negishi, I., Ogasawara, K., Uede, T., Onoe, K.: "Defective development of NK1.1+ T-cell antigen receptor alphabeta+ cells in zeta-associated protein 70 null mice with an accumulation of NK1.l+ CD3-NK-like cells in the thymus."Blood. 97(6). 1765-1775 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nagamori, M., Kawaguchi, S., Murakami, M., Wada, T., Nagoya, S., Yamashita, T., Inobe, M., Uede, T.: "Intrinsic and extrinsic manipulation of B7/CTLA-4 interaction for induction of anti-tumor immunity against osteosarcoma cells."Anticancer Res. 22(6A). 3223-3227 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ohshima, S., Yamaguchi, N., Nishioka, K., Mima, T., Ishii, T., Umeshita-Sasai, M., Kobayashi, H., Shimizu, M., Katada, Y., Wakitani, S., Murata, N., Nomura, S., Matsuno, H., Katayama, R., Kon, S., Inobe, M., Uede, T., Kawase, I., Saeki, Y.: "Enhanced local production of osteopontin in rheumatoid joints."J Rheumatol. 29(10). 2061-2067 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsuji, H., Kawaguchi, S., Wada, T., Nagoya, S., Inobe, M., Yamashita, T., Ishii, S., Uede, T.: "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(9). 747-755 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nagamori, M., Kawaguchi, S., Murakami, M., Wada, T., Inobe, M., Ishii, S., Uede T.: "In vivo immunogenicity of osteosarcoma cells that express B7-1a, an alternatively spliced form of B7-1."Anticancer Res. 22(4). 2009-2013 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kimura, F., Gotoh, M., Tanaka, T., Luo, Z., Miyazaki, J., Uede, T., Monden, M., Miyasaka, M.: "Locally expressed CTLA4-Ig in a pancreatic beta-cell line suppresses accelerated graft rejection response induced by donor-specific transfusion."Diabetologia. 45(6). 831-840 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shiraishi, T., Yasunami, Y., Takehara, M., Uede, T., Kawahara, K., Shirakusa, T.: "Prevention of acute lung allograft rejection in rat by CTLA4Ig."Am J Transplant. 2(3). 223-228 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Konishi, K., Inobe, M., Yamada, A., Murakami, M., Todo, S., Uede, T.: "Combination treatment with FTY720 and CTLA4IgG preserves the respiratory epithelium and prevents obliterative disease in a marine airway model."J Heart Lung Transplant.. 21(6). 692-700 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Chiba, S., Okamoto, H., Kon, S., Kimura, C., Murakami, M., Inobe, M., Matsui, Y., Sugawara, T., ShimiZu, T., Uede, T., Kitabatake, A.: "Development of atherosclerosis in osteopontin transgenic mice."Heart Vessels. 16(3). 111-117 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nomura, M., Yamashita, K., Murakami, M., Takehara, M., Echizenya, H., Sunahara, M., Kitagawa, N., Fujita, M., Furukawa, H., Uede, T., Todo, S.: "Induction of donor-specific tolerance by adenovirus-mediated CD40Ig gene therapy in rat liver transplantation."Transplantation. 73(9). 1403-1410 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsuchida, Y., Usui, M., Uede, T.: "Vascularized bone-marrow allotransplantation in rats prolongs the survival of simultaneously grafted alloskin."J Reconstr Microsurg. 18(4). 289-294 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ohshima, S., Kobayashi, H., Yamaguchi, N., Nishioka, K., Umeshita-Sasai, M., Mima, T., Nomura, S., Kon, S., Inobe, M., Uede, T., Saeki, Y.: "Expression of osteopontin at sites of bone erosion in a marine experimental arthritis model of collagen-induced arthritis : possible involvement of osteopontin in bone destruction in arthritis."Arthritis Rheum. 46(4). 1094-1101 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Matsui, Y., Inobe, M., Okamoto, H., Chiba, S., Shimizu, T., Kitabatake, A., Uede, T.: "Blockade of T cell costimulatory signals using adenovirus vectors prevents both the induction and the progression of experimental autoimmune myocarditis."J Mol Cell Cardiol. 34(3). 279-295 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yumoto, K., Ishijima, M., Rittling, SR., Tsuji, K., Tsuchiya, Y., Kon, S., Nifuji, A., Uede, T., Denhardt, DT., Noda, M.: "Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice."Proc Natl Acad Sci U S A. 99(7). 4556-4561 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kim, JH., Skates, SJ., Uede, T., Wong, Kk KK., Schorge, JO., Feltmate, CM., Berkotivitz, RS., Cramer, DW., Mok, SC.: "Osteopontin as a potential diagnostic biomarker for ovarian cancer."JAMA. 287(13). 1671-1679 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iwasaki, N., Gohda, T., Yoshioka, C., Murakami, M., Inobe, M., Minami, A., Uede, T.: "Feasibility of immunosuppression in composite tissue allografts by systemic administration of CTLA4Ig."Transplantation. 73(3). 334-340 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Koguchi, Y., Kawakami, K., Kon, S., Segawa, T., Maeda, M., Uede, T., Saito, A.: "Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells."Infect Immun. 70(3). 1042-1048 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kon, S., Yokosaki, Y., Maeda, M., Segawa, T., Horikoshi, Y., Tsukagoshi, H., Rashid, MM., Morimoto, J., Inobe, M., Shijubo, N., Chambers, AF., Uede, T.: "Mapping of functional epitopes of osteopontin by monoclonal antibodies raised against defined internal sequences."J Cell Biochem. 84(2). 420-432 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamashita, K., Masunaga, T., Yanagida, N., Takehara, M., Hashimoto, T., Kobayashi, T., Echizenya, H., Hua, N., Fujita, M., Murakami, M., Furukawa, H., Uede, T., Todo, S.: "Long-term acceptance of rat cardiac allografts on the basis of adenovirus mediated CD40Ig plus CTLA4Ig gene therapies."Transplantation. 76(7). 1089-1096 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Saeki, Y., Mima, T., Ishii, T., Ogata, A., Kobayashi, H., Ohshima, S., Ishida, T., Tabunoki Y., Kitayama, H., Mizuki, M., Katada, Y., Asaoku, H., Kitano, M., Nishimoto, N., Yoshizaki, K., Maeda, M., Kon, S., Kinoshita, N., Uede, T., Kawase, I.: "Enhanced production of osteopontin in multiple myeloma : clinical and pathogenic implications."Br J Haematol. 123(2). 263-270 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsuji, H., Kawaguchi, S., Wada, T., Nagoya, S., Inobe, M., Yagita, H., Okumura, K., Yamashita, T., Uede, T.: "Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer."Cancer Gene Ther. 10(9). 717-725 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamamoto, N., Sakai, F., Kon, S., Morimoto, J., Kimura, C., Yamazahi, H., Okazaki, I., Seki, N., Fujii, T., Uede, T: "Essential role of the cryptic epitope SLAYGLR within osteopontin in a marine model of rheumatoid arthritis."J Clin Invest. 112(2). 181-188 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yagi, J., Arimam, Y., Dianzani, U., Uede, T., Okamoto, T., Uchiyama, T.: "Regulatory roles of IL-2 and IL-4 in H4/inducible costimulator expression on activated CD4+ T cells during Th cell development."J Immunol. 171(2). 783-794 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Futamatsu, H., Suzuki, J., Kosuge, H., Yokoseki, O., Kamada, M., Ito, H., Inobe, M., Isobe, M., Uede, T.: "Attenuation of experimental autoimmune myocarditis by blocking activated T cells Through inducible costimulatory molecule pathway."Cardiovasc Res. 59(1). 95-104 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tosa, N., Murakami, M., Jia, WY., Yokoyama, M., Masunaga, T., Iwabuchi, C., Inobe, M., Iwabuchi, K., Miyazaki, T., Onoe, K., Iwata, M., Uede, T.: "Critical function of T cell, death-associates gene 8 in glucocorticoid-induced thymocyte apoptosis."Int Immunol. 15(6). 741-749 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Matsui, Y., Rittling, SR., Okamoto, H., Inobe, M., Jia, N., Shimizu, T., Akino, M., Sugawara, T., Morimoto, J., Kimura, C., Kon, S., Denhardt, D., Kitabatake, A., Uede, T.: "Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice."Arterioscler Thromb Vasc Biol. 23(6). 1029-1034 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Matsui, Y., Okamoto, H., Inobe, M., Jia, N., Shimizu, T., Akino, M., Sugawara, T., Tezuka, K., Nakayama, Y., Morimoto, J., Kimura, C., Kon, S., Miyazaki, T., Kitabatake, A., Uede, T.: "Adenovirus-mediated gene transfer of ICOSIg fusion protein ameliorates ongoing experimental autoimmune myocarditis."Hum Gene Ther. 14(6). 521-532 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kosuge, H., Suzuki, J., Gotoh, R., Koga, N., Ito, H., Isobe, M., Inobe, M., Uede, T.: "Induction of immunologic tolerance to cardiac allograft by simultaneous blockade of inducible co-stimulator and cytotoxic T-lymphocyte antigen 4 pathway."Transplantation. 75(8). 1374-1379 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Salama, AD., Yuan, X., Nayer, A., Chandraker, A., Inobe, M., Uede, T., Sayegh, MH.: "Interaction between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmune responses in vivo."Am J Transplant. 3(4). 390-395 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kanaya, K., Tsuchida, Y., Inobe, M., Murakami, M., Hirose, T., Kon, S., Kawaguchi, S., wada, T., Yamashita, T., Ishii, S., Uede, T.: "Combined gene therapy with adenovirus vectors containing CTLA4Ig and CD40Ig・prolongs survival of composite tissue allografts in rat model."Transplantation. 75(3). 275-281 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Koguchi, Y., Kawakami, K., Uezu, K., Fukushima, K., Kon, S., Maeda, M., Nakamoto, A., Owan, I., Kuba, M., Kudeken, N., Azuma, M., Yara, S., Shinzato, T., Higa, F., Tateyama, M., Kadota, J., Mukae, H., Kohno, S., Uede, T., Saito, A.: "High plasma osteopontin level and its relationship with interleuhin-12-Mediated type 1 T helper cell response in tuberculosis."Am J Respir Crit Care Med. 167(10). 1355-1359 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Morimoto, J., Inobe, M., Kimura, C., Kon, S., Diao, H., Aoki, M., Miyazaki, T., Denhardt, D.T., Rittling, S., Uede, T.: "Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms."Int Immunol. 16(3). 477-488 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishii, T., Ohshima, S., Ishida, T., Kawase, I., Mima, T., Tabunoki, Y., Kobayashi, H., Maeda, M., Uede, T., Liaw, L., Kinoshita, N., Saeki, Y.: "Mice with osteopontin deletion remain predisposed to collagen-induced arthritis."Arthritis Rheum. 50(2). 669-671 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tanaka, K., Morimoto, J., Kon, S., Kimura, C., Inobe, M., Diao, H., Hirschfeld, G., Weiss, JM., Uede, T.: "Effect of osteopontin alleles on beta-glucan-induced granuloma formation in the mouse liver."Am J Pathol. 164(2). 567-575 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ono, E., Amagai, K., Yoshino, S., Taharaguchi, S., Inobe, M., Uede, T.: "Resistance to pseudorabies virus infection in transformed cell lines expressing a soluble form of porcine herpesvirus entry mediator C."J Gen Virol. 85(1). 173-178 (2004)
  • Description: 「研究成果報告書概要(欧文)」より