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The effect of Th1/Th2 dominance on the clinicopathological feature in murine model of IgA nephropathy

Research Project

Project/Area Number 09671162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MUSO Eri  Kyoto University, Cardiovascular Medicine, Lecturer, 医学研究科, 講師 (10190852)

Co-Investigator(Kenkyū-buntansha) ONO Takahiko  Kyoto University, Cardiovascular Medicine, Assistant, 医学研究科, 助手 (60243028)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsIgA Nephropathy / TGF-beta / HIGA mouse / Th1 / Th2 / IL-12 / IL-4 / IFN-gamma / crescent formation
Research Abstract

Introduction :
In IgA nephropathy patients, although the Th1 and Th2 predominance has long been investigated, the results obtained are controversial. In order to investigate the immunoregulatery background which promotes both active proliferative and chronic sclerotic lesions in IgA nephropathy, Th1/Th2 balance and the effect of Th1 bias by administration of IL12 were assessed in high IgA prone murine model (HIGA mouse) which has recently been established by selective mating of high serum IgA ddY mice and exerts early and spontaneously high serum IgA with progressive mesangial sclerosis accompanying elevated renal expression of TGFbeta and matrix protein mRNAs.
Methods and Results :
1) In 14 and 28 week-old HIGA mice and age-matched C57BL/6 and Balb/c mice as Th1 and Th2 predominant control, respectively, the production of TFNgamma IL-4 and TGFb1 by spleen T cells stimulated by PMA and PHA were measured. In HIGA mice, the elevation of IFNgamma and TGFbeta1 production with the relative increase of IL-4 with age from spleen CD4+T cells were shown.
2) For 31-34 week old HIGA mice, recombinant murine 100 , 300ng IL-12 and PBS as control were administered intraperitoneally and the change of serum IgA and renal lesions were assessed. Th1 bias by short term IL-12 administration induced cellular crescent formation and interstitial cell infiltration with macrophage invasion which accompanied upregulation of local TGFbeta1 mRNA expression., while serum IgA elevation was significantly suppressed.
Conclusion :
In murine model of IgA nephropathy, active inflammatory lesion may relate with the dominance of Th1 and progressive glomerular and renal sclerosis may be promoted by latently upregulated Th2.

Report

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

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Muso E, et al: "The effect of Th1/Th2 dominance on the clinicopathological feature of human and murine model of IgA nephropathy." Proceeding of 4eme Symposium Franco-Japonais de Nephrologie. (in print). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono T, et al: "Inhibitory effects of the herbal medicine Saiboku-to on the proliferation of cultured murinemesangial cells." Nephrology. 4. 367-372 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muso E, et al: "Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA dd,Y mice." Kidney International. 50. 1946-1957 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 武曾 惠理 他: "特集"IgA腎症30年"、 動物実験による新しい知見・展望." 腎と透析. 46. 107-112 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 武曾 惠理: "Annual Review 腎臓 1997" 中外医学社, 5 (52〜56) (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muso E,et al: "The effect of Th1/Th2 dominance on the clinicopathological feature of human and murine model of IgA nephropathy." Proceeding of 4eme Symposium Franco-Japonais de Nephrologie. (in print). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono T,et al: "Inhibitory effects of the herbal medicine Saiboku-to on the proliferation of cultured murine mesangial cells." Nephrology. 4. 367-372 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muso E,et al: "Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice." Kidney International. 50. 1976-1957 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muso E,et al: "New horizon of exprimental and spontaneous animal of IgA nephropathy." Kidney and Dialysis. 46. 107-112 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muso E: "Annual Review Kidney 1997." Cyu-gai Igakusha. 52-56 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kamata,T et al: "Up-regulation glomerular extracellurar matrix and transforming growth factor-β expression in RF/J mice." Kidney International. 55. 864-876 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Muso E,et al: "The effect of Th1/Th2 dominance on the clinicopathological feature of human and murine model of IgA nephropathy." 4eme Symposium Franco-Japonais de Nephrologie. (in print). (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nogaki F,et al: "Age-associated relative shift to Th2 predominance and the effects of IL-12 administration in high IgA strain of ddY mice." Nephrology. 4 (supple). A41 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Haku E,et al: "Whole-Blood interferon-producing capacity in IgA nephropathy patients." Nephrology. 3 (supple). A14 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyawaki S,et al: "Selective breeding for high serum IgA levels from noninbred ddY mice : Isolation of a strain with an early onset of glomerular IgA deposition." Nephron. 76. 201-207 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Muso E,et al: "Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice." Kidney International. 50. 1946-1957 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小林 いけい 他: "IL-12投与による血清IgAクロノタイプの変化;若年好発生純系好IgA血症(HIGA)マウスにおける検討" Pharma Medica. 17 (2). 212-214 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 武曽 恵理 他: "特集“IgA腎症30年"、動物実験による新しい知見・展望" 腎と透析. 46. 107-112 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 牧野 利明 他: "ddYマウス自然発症IgA腎症モデルを用いた紫蘇の糸球体腎炎抑制作用の検討" 和漢医薬学雑誌. 14. 420-421 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 武曾 恵理: "Annual Review腎臓1997" 中外医学社, 5 (52〜56) (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oyama A, et al.: "Upregulated TGF-β mRNA expression in the spleen T cells of high IgA prone inbred(HIGA)mice,a murine model of IgA nephropathy with glomerulosclerosis." Kidney Int. (in print). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawamura T, et al.: "Deposition of fibronectin markedly increase in Th endothelial side of thickened glomerular basement membrane in high serum IgA ddY(HIGA)mice." Journal of American Society of Nephrology. 8(9). 519A (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nogaki F, et al.: "Age associating relative shift to Th2 predominance with elevation of IL-4 and TGF-β production of CD4_+ spleen cells from hifh IgA strain(HIGA)of ddY mice." Journal of American Society of Nephrology. 8(9). 462A (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Haku E, et al.: "Whole blood interferon-producing capacities(IFN-PCs)in clinically stable IgA nephropathy(IgA-N)patients." Journal of American Society of Nephrology. 8(9). 536A (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Imasawa T, et al.: "Etiopathogenesis of IgA nephropathy may lie in disordered hemopoietic stem cells." Journal of American Society of Nephrology. 8(9). 498A (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyawaki S, et al.: "Selective breeding for high serum IgA levels from noninbred ddY mice:Isolation of a strain with an early onset of glomerular IgA deposition." Nephron. 76. 201-207 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 武曾惠理: "Annual Review 腎臓1997" 中外医学社, 52-56 (1997)

    • Related Report
      1997 Annual Research Report

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

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