| Project/Area Number |
09671168
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
FUKUDA Kyoichi (1998-1999) Faculty, of Medicine, KYUSHU UNIVERSITY Research Associate, 医学部, 助手 (90294925)
安藤 高志 (1997) 九州大学, 医学部, 助手 (40281191)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAKATA Hideki Faculty, of Medicine, KYUSHU UNIVERSITY Ass.Prof., 医学部, 助教授 (70181146)
KISHIHARA Kenji Medical Institute of Bioregulation, KYUSHU UNIVERSITY Research Associate, 生体防御医学研究所, 助手 (80214774)
福田 恭一 九州大学, 医学部, 助手 (90294925)
滝本 博明 九州大学, 生体防御医学研究所, 助手 (00253534)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Knockout mouse / Tubulointerstitial damage / Cellular immunity / Cytokine / T cell receptor |
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| Research Abstract |
Tubulointerstitial damage is known to play an important role in progressive renal diseases. However, the role of interstitial infiltrating cells remains to be clarified. Thus, we designed this study to elucidate immunological mechanisms in tubulointerstitial damage. For this purpose, histological examination was performed in the obstructed kidneys of knockout (KO) mice with unilateral ureteral obstruction (UUO). The flowcytometry of infiltrating cells from the obstructed kidney of normal mouse showed that interstitial infiltrating cells were predominantly macrophages. The tubulointerstitial damages in obstructed kidneys of both CD4 KO mouse and CD8 KO mouse after UUO were not significantly different from those of control mice. These results implied that the major players are macrophages rather than T cells in the setting of UUO.However, the tubulointerstitial damages in obstructed kidneys of nude mice were clearly milder than hose of control mice, suggesting that the cellular immunity with T cells, namely a system in which Th1 cells activate macrophages, is involved in the tubulointerstitial damages. Since TNF-α is well-know important effecter molecule of Th1 cell, we prepared the mice, bone marrow-derived cells of which have not any TNF-α receptors, using adult thymectomy (ATX) followed by bone marrow transplantation from TNF-α receptor KO mouse, i.e. ATX-BM chimera mouse, and performed histological examination after UUO.This result revealed that the tubulointerstitial damages in obstructer kidneys of ATX-BM chimera mice were milder than those of control mice. Taken together, our results suggest that the activation of macrophages by cytokines such as TNF-α derived from T cells play a major role in tubulointerstitial damage.
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