1998 Fiscal Year Final Research Report Summary
The effect of Th1/Th2 dominance on the clinicopathological feature in murine model of IgA nephropathy
| Project/Area Number |
09671162
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
MUSO Eri Kyoto University, Cardiovascular Medicine, Lecturer, 医学研究科, 講師 (10190852)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Takahiko Kyoto University, Cardiovascular Medicine, Assistant, 医学研究科, 助手 (60243028)
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| Project Period (FY) |
1997 – 1998
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| Keywords | IgA Nephropathy / TGF-beta / HIGA mouse / Th1 / Th2 / IL-12 / IL-4 / IFN-gamma / crescent formation |
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| 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.
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