2001 Fiscal Year Final Research Report Summary
THE STUDY OF THE MECHANISMS AND TREATMENT OF RENAL INTERSTITIAL FIBROSIS USING INFLAMED SITE-SPECIFIC GENE DELIVERY.
| Project/Area Number |
11671055
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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 | JIKEI UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
UTSUNOMIYA Yasunori JIKEI UNIVERSITY SCHOOL OF MEDICINE, THE MEDICAL DEPARTMENT, LECTURER, 医学部, 講師 (70231181)
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| Project Period (FY) |
1999 – 2001
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| Keywords | RENAL INTERSTITIAL FIBROSIS / GENE DELIVERY / ICAM-1 / INTERLEUKIN-1 / BONE MARROW CELLS / MACROPHAGE |
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| Research Abstract |
In this study, we used genetically modified bone marrow-derived CD11b^+CD18^+ vehicle cells to deliver IL-1 receptor antagonist (IL-ira) for treatment of inflamed, renal interstitium in an animal model of unilateral ureteral obstruction (UUO). Vehicle cells that expressed the ICAM-1 ligands, CD11b and CD 18, were obtained from bone marrow cells of DBAJ2j mice and adenovirally transduced with the IL-ira gene or glucocerebrosidase (GC) gene ex vivo. In kidneys treated to develop UUO, levels of ICAM-i, IL-1β and IL-1 receptor expression increased within 3 days compared to coniralateral untreated kidneys in the same mice. Similarly, the macrophage infiltration in the cortical interstitium increased after 3 days in UUO kidneys, but not untreated kidneys. After UUO developed, DBA/2j mice were injected intravenously with either IL-1ra^+ vehicle cells (IL-1ratreated mice) or GC vehicle cells (OC-treated mice) at 24 hours after UUO. Six days after the injection of these vehicle cells, marked increased of CD11b^+IL-1ra^+ vehicle cells were observed in the ICAM-1-positive interstitium of UUO kidneys from ILira-treated mice. In contrast, no CD11b^+ IL-1ra^+ cells appeared in ICAM-i-negative contralateral kidneys from these mice. Furthermore, the infiltration of macrophages (p<0.001), expression of ICAM-1 (p<z0.005), and presence of a-smooth muscle actin (p=0.005) in the interstitium of UUO kidneys was significantly decreased in IL-ira-treated mice compared to GC-treated mice. These fmdings suggest that IL-1 may contribute to the development of renal interstitial injury and that our method can deliver a functioning gene encoding an anti-inflammatory cytokine gene specifically at that site by interacting with local adhesion molecules.
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[Publications] Yokoo T, Ohashi T, Utsunomiya Y, Kojima H, Imasawa T, Kogure T, Hisada Y, Okabe M, Eto Y, Kawamura T, Hosoya T: "Prophylaxis of antibody-induced acete glomerulonephritis with genetically modified bone marrow-derived vehicle cells."Hum Gene Ther. 10. 2673-2678 (1999)
Description
「研究成果報告書概要(欧文)」より
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