| Project/Area Number |
14570193
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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 |
Experimental pathology
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| Research Institution | Nagasaki University |
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Principal Investigator |
SHICHIJO Kazuko Nagasaki University, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (90136656)
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| Co-Investigator(Kenkyū-buntansha) |
SEKINE Ichiro Nagasaki University, Professor, 大学院・医歯薬学総合研究科, 教授 (60039922)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | radiation colitis / ulcerative colitis / spontaneously hypertensive rats / colitis / eosinophil cationic protein / interleukin-11 / nuclear dust / apoptosis / Eosinophil cationic protein / 放射性腸炎 / DSS腸炎 / GVHD / インターロイキン-11 / ポラポレジンク / 放射線腸炎 / 酢酸胃潰瘍 / アポトーシス / ケフィア / マクロファージ |
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| Research Abstract |
To explore the molecular pathology of intractable colitis and produce new therapeutic drugs, molecular mechanism on disregulation of apoptotic machinery was studied in 1)ulcerative colitis and 2)radiation colitis models. Moreover, it was determined whether interleukin-11, which is a multifunctional 20-kd hematopoietic growth factor cloned from an immortalized primate bone marrow stromal cell line, and some drugs are effective on these colitis.
1.Susceptibility to X ray whole body irradiation induced apoptosis of crypt cells on sympathetic hyperfunction in spontaneously hypertensive rats
2.Radiation colitis model induced by the exposure of 22.5 Gy X ray to the colon.
3.Ulcer development and healing process of dextran sulfate sodium (DSS) colitis as a model of ulcerative colitis.
4.Nuclear dust within the lamina propria beneath the basement membrane of epithelium in biopsies of patient with colitis
5.Donor-derived keratinocytes and severity of graft-versus-host disease (GVHD) in epidermis.
6.M
… More
olecular pathology : i)mucosal epithelium injury and ulcer, ii)apoptosis of colonic mucosa by TUNEL method and analysis by NIH image, iii)immunohistochemistry and Western blotting for caspase-3, Ki-67 and ED1
These results demonstrated that the hyperfunction of sympathetic nervous system caused hypersusceptibility to radiation induced apoptosis of crypt cells, which inhibited by the treatment of Keffia. Keffia have shown to protect colonic stem cells. Interleukinn-11 inhibited the radiation colitis. The nuclear dust in biopsies of patients with colitis correlated with inflammation, eosinophil infiltration, edema and congestion. Nuclear dust increased in DSS colitis, and decreased by interleukin-11 treatment. Eosinophil cationic protein antibody treatment suppressed DSS colitis and accelerated colonic epithelium regeneration. Donor-derived keratinocytes were identified in epidermis of GVHD. Donor-derived colonocytes might express in patients with colitis. We demonstrated here disregulation of apoptotic machinery in intractable colitis. Intervention directed towards the apoptotic process may prove beneficial in the treatment of colitis. Less
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