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CERAMIDE,APOPTOSIS-INDUCING SECOND-MESSENGER,USED IN THE TREATMENT OF LUPUS-PRONE MODEL MICE

Research Project

Project/Area Number 09670490
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionJICHI MEDICAL SCHOOL

Principal Investigator

MINOTA Seiji  JICHI MEDICAL SCHOOL,DEPARTMENT OF MEDICINE,PROFESSOR, 医学部, 教授 (30211593)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsSYSTEMIC LUPUS ERYTHEMATOSUS / MOUSE / APOPTOSIS / TREATMENT / CERAMIDE / FTY720
Research Abstract

Upon ligation with Fas-ligand, cell-surface Fas transmits apoptosis-signals in lymphocytes and cerarnide is considered to act as a second messenger in this pathway. We reported last year that oral administration of a novel immunosuppressant FTY72O, which has a very close structural similarity with ceramide, successfully improved glomerulonephritis and prolonged survival rates of lupusprone MRL-lpr/lpr mice. The purpose of the study this year, therefore, is to examine whether ceramide itself could be used for treatment of MRL-lpr/lpr mice when administered orally.
Because ceramides with long side-chains can not penetrate cell membranes and induce apoptosis in vitro, we selected cell-permeable C2-ceramide in this study. Two mgfkg body weight of C2-ceramide dissolved in olive-oil were administered orally three times a week to 15 MRL-lpr/lpr mice of 4-month old. The same number of MRL-lpr/lpr mice was received either olive-oil alone as a negative control or dexamethasone (2 mg/kg) as a positive control for treatment. Anti-DNA antibody titer in sera, survival curve and renal pathology were examined for the efficacy of the treatments.
At the age of eight months, MRL-lpr/lpr mice treated with C2-ceramide showed a longer survival curve, decreased number of T cells with a CD^<3+>CD^<4->CD^<8-> phenotype, and a lower level of serum anti-DNA antibody than those treated with olive-oil alone. These parameters were all statistically signficant. IgG deposited in glomeruli from mice treated with C2-ceramide was far less than that from mice administered with olive-oil alone. Level of these mprovements induced by oral C2-ceramide was almost comparable with that induced by dexamethasone. Liver damage and hyperglycemia which were desasterous side-effects of systemic anti-Fas antibody and dexamethasone administration, respectively, were not observed.
C2-ceramide seems to deserve further attention for a possible therapeutic regimen with less side-effect.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Iwamoto, M., Minota, S., et: "Early diagnosis of takayasu's arteritis using gadolinium-contrasted magnetic resonance imaging" Arthritis Rheum.in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuyama, J., Minota, S.et al: "Characterization of the 4C8 antigen involved in transendothelial migration of CD26hi T cells after tight adhesion to human umbilical vein cell monolayers" J.Exp.Med.in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshio, T., Masuyama, J., Minota, S., et al: "A Close Temporal Relationship of Liver Disease to Anti ribosomal PO Protein Antibodies and Central Nervous System Disease in Patients with Systemic Lupus Erythematosis" J.Rheumatol.25. 681-688 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kamimura, T., Minota S.et al: "Acute acalculous cholecystitis in systemic lupus erythematosus : a case report and review of the literature" Lupus. 7. 361-363 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirata, D., Minota, S.et al: "Preferential binding with Echerichia coli hsp60 of antibodies prevalent in sera from patients with theumatoio arthritis" Clin.Immunol.Immunopathol.82. 141-148 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Horie, S., Minota, S.et al: "Detection of Large Macrophage Colony Forming Cells in the Pe-ripheral Blood of Patients with Rheumatoid Arthritis." J.Rheumatol.24. 1517-1521 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwamoto, M., Minota, S., et al: "Early diagnosis of takayasu's arteritis using gadolinium-contrasted magnetic resonance imaging" Arthritis Rheum.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuyama, J., Minota, S.et al: "Characterization of the 4C8 antigen involved in transendothelial migration of CD26hi T cells after tight adhesion to human umbilical vein cell monolayers" J.Exp.Med.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirata, D., Kaneko, N., Iwamoto, M., Yoshio, T., Okazaki, .H,Mimori, A., Masuyama, J.and Minota, S.: "Infection with an unevelopes DNA virus (TTV) associated with non-A to G hepatitis in patients with theumatoid arthritis" Br J Rheumatol. 37 (12). 1361-1362 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshio, T., Masuyama, J., Minota, S., et al: "A Close Temporal Relationship of Liver Disease to Anti ribosomal P0 Protein Antibodies and Central Nervous System Disease in Patients with Systemic Lupus Erythematosis" J.Rheumatol.25. 681-685 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshio, T., Masuyama, J., Iwamoto, M., Mimori, A., Takeda, A., Okazaki, H., Kano, S.and Minota, S.: "Purity of synthetic ribosomal P peptides in enzyme-linked immunosorbent assay : comment on the article by Yoshio et al. Reply." Arthritis Rheum.41 (6). 1138 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kamimura, T., Mimori, A., Tadeda, A., Masuyama, J., Yoshio, T., Okazaki, H., Kano, S.and Minota, S.: "Acute acalculous cholecystitis in systemic lupus erythematosus : a case report and review of the literature" Lupus. 7. 361-363 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshio, T., Masuyama, J-I., Minota, S., Iwamoto, M., Mimori, A., Takeda, A., Okazaki, H., and Kano, S.: "Correlation of serum IgG antibodies to recombiant P0 fusion protein with IgG antibodies to carboxyl-terminal 22 syntheric peptides and carboxyl-terminal 22 amino acid-depleted recombinant P0 fusion protein in patients with systemic lupus erythematos" Arthritis Rheum.40. 1364-1365 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshio, T., Masuyama, J-I., Kohda, N., Hirata, D., Sato, H., Iwamoto, M., Mimori, A., Takeda, A., Minota, S.and Kano, S.: "Association of interleukin 6 release from endothelial cells and pulmanary hypertention in SLE." J.Rheumatol.24. 489-495 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirata, D., Hirai, I., Iwamoto, M., Yoshio, T., Takeda, A., Masuyama, J., Mimori, A., Kano, S., and Minota, S.: "Preferential binding with Echerichia coli hsp60 of antibodies prevalent in sera from patients with rheumatoio arthritis" Clin.Immunol.Immunopathol.82. 141-148 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mimura, T., Minota, S., Nojima, Y., Morino, N., Hamasaki, K., Furuya, H.and Yazaki, Y.: "Constitutive Tyrosine Phosphorylation of the vav Proto-Oncogene Product in MRL/Mp-lpr/lpr Mice." J.Immunol.158. 2977-2983 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Horie, S., Nakada, K., Masuyama, J., Yoshio, T., Minota, S., Wakabayashi, Y., Hirose, S., and Kano, S.: "Detection of Large Macrophage Colony Forming Cells in the Peripheral Blood of Patients with Rheumatoid Arthritis." J.Rheumatol.24. 1517-1521 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwamoto,M.,Minota,S.,et al: "Early diagnosis of takayasu's arteritis using gadolinium-contrasted magnetic resonance imaging" Arthritis Rheum.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masuyama,J.,Minota,S.et al: "Characterization of the 4C8 antigen involved in transendothelial migration of CD26hi T cells after tight adhesion to human umbilical vein cell monolayers" J.Exp.Med.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshio,T.,Masuyama,J.,Minota,S.,et al: "A Close Temporal Relationship of Liver Disease to Anti ribosomal P0 Protein Antibodies and Central Nervous System Disease in Patients with Systemic Lupus Erythematosis" J.Rheumatol.25. 681-688 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kamimura,T.,Mimori,A.,Tadeda,A.,Masuyama,J.,Yoshio,T.,Okazaki,H.,Kano,S.and Minota,S.: "Acute acalculous cholecystits in systemic lupus erythematosus:a case report and review of the literature" Lupus. 7. 361-363 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirata,D.,Hirai,I.,Iwamoto,M.,Yoshio,T.,Takeda,A.,Masuyama,J.,Mimori,A.,Kano,S.,and Minota,S.: "Preferential binding with Echerichia coli hsp60 of antibodies prevalent in sera from patients with rheumatoio arthritis" Clin.Immunol.Immunopathol.82. 141-148 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Horie,S.,Nakada,K.,Masuyama,J.,Yoshio,T.,Minota,S.,Wakabayashi,Y.,Hirose,S.,and Kano,S.: "Detection of Large Macrophage Colony Forming Cells in the Pe-ripheral Blood of Patients with Rheumatoid Arthritsi." J.Rheumatol.24. 1517-1521 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikeda,M., Minota,S., and Kano,S.: "Regulation of MHC class I expression by inflammatory cytokines in rat mesangial cells." Nephron. 76. 90-95 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirata,D., Hirai,I., Iwamoto,M., Yoshio,T., Takeda,A., Masuyama,J., Mimori,A., Kano,S., and Minota,S.: "Preferential binding of Escherichia coli hsp60 of antibodies prevalent in sera from patients with rheumatoid arthritis." Clin.Immunol.Immunopathol.82. 141-148 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikeda,M., Ikeda,U., Shimada,K., Fujita,N., Okada,K., Saito,T., Minota,S., and Kano,S.: "Tranilast inhibits the growth of rat mesangial cells." Eur J Pharmacol.324. 283-287 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshio,T., Masuyama,J., Kohda,N., Hirata,D., Sato,H., Iwamoto,M., Mimori,A., Takeda,A., Minota,S., and Kano,S.: "Association of Interleukin 6 Release from Endothelial Cells and Pulmonary Hypertension in SLE." J.Rheumatol.24. 489-495 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mimura,T., Minota,S., Nojima,Y., Morino,N., Hamasaki,K., Furuya,H., and Yazaki,Y.: "Constitutive Tyrosine Phosphorylation of the vav Proto-Oncogene Product in MRL/Mp-lpr/lpr Mice." J.Immunol.158. 2977-2983 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Horie,S., Nakada,K., Masuyama,J., Yoshio,T., Minota, S., Wakabayashi,Y., Hirose,S., and Kano,S.: "Detection of Large Macrophage Colony Forming Cells in the Peripheral Blood of Patients with Rheumatoid Arthritis." J.Rheumatol.24. 1517-1521 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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