Therapeutic potential of regulation of apoptosis for resolution of inflammation
| Project/Area Number |
17591076
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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 |
Pediatrics
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
BABA Atsushi (2006) SHINSHU UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF PEDIATRICS, 医学部, 助手 (00324252)
安井 耕三 (2005) 信州大学, 医学部小児医学, 助教授 (90200493)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAMOTO Masaya SHINSHU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DIVISION OF IMMUNOLOGY AND INFECTIOUS DISEASES, 大学院医学研究科, 講師 (90226928)
馬場 淳 信州大学, 医学部小児医学, 助手 (00324252)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | apoptosis / inflammation / neutrophil / reactive oxygen species / superoxide dismutase / 血球貧食症候群 / レドックス制御 / 喘息 / 炎症 / ショック / サイトカイン / β2刺激薬 / 好中球性炎症 |
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| Research Abstract |
Neutrophils are short-lived leukocytes that must be removed safely by apoptosis. Neutrophils generate reactive oxygen species (ROS) spontaneously, increasing oxidative stress, which triggers the metabolic cascade and leads to the activation of caspase 3, 8 and 9 in neutrophils, and then induces their apoptosis. Our observations suggested that both ROS-and Fas-mediated apoptosis of human neutrophils occur in a caspase-3-dependent manner, and that hydrogen peroxide may be a major mediator of ROS-mediated neutrophil apoptosis augmented by extracellular superoxide dismutase (SOD). The generation of superoxide anions may not be a direct mediator of neutrophil apoptosis. It is possible that apoptosis could be processed not only by microbial invasion and primary bactericidal action but also by enzymatic modification, involving SOD activation. During the acute phases of microbial invasion, bactericidal ability must be preserved and the apoptotic process should be retarded. Human macrophages ge
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nerate GM-CSF and/or express high levels of catalase activity, which may protect against apoptotic signals in neutrophils and exhibit marked neutrophil-mediated defensive actions. Neutrophil apoptosis represents a crucial step in the mechanism governing the resolution of inflammation and has been suggested as a possible target for the control of neutrophil-mediated tissue injury. However, not only in neutrophils but also in other cells/tissues, systemically administered SOD may increase hydrogen peroxide that sometimes plays a role as a second messenger in the production of inflammatory cytokines. In such conditions, the extracellular combination with SOD of hydrogen scavenging compounds like catalase, glutathione peroxidase and peroxiredoxin may be more beneficial in the aspect of protection against oxidative stress. Although further studies are needed to elucidate the mechanisms of this pathway and the pathology of various inflammatory conditions, SOD may represent a novel therapeutic approach for the ROS-dependent tissue damage induced by neutrophils via several mechanisms. Less
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Report
(3 results)
Research Products
(22 results)
