Comprehensive regulatory system of PAMPs/DAMPs by TM-PC/EPCR system
Project/Area Number |
24659798
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Emergency medicine
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Research Institution | Kagoshima University |
Principal Investigator |
MARUYAMA Ikuro 鹿児島大学, 大学院・医歯学総合研究科, 特任教授 (20082282)
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Co-Investigator(Kenkyū-buntansha) |
ITO Takashi 鹿児島大学, 大学院・医歯学総合研究科, 特任講師 (20381171)
TERUTO Hashiguchi 鹿児島大学, 大学院・医歯学総合研究科, 教授 (70250917)
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Co-Investigator(Renkei-kenkyūsha) |
KAWAHARA Ko-ichi 大阪工業大学, 工学部生命工学科, 特任教授 (10381170)
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Research Collaborator |
YAMADA Shingo 株式会社シノテスト
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Project Period (FY) |
2012
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Project Status |
Completed (Fiscal Year 2012)
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Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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Keywords | PAMPs / DAMPs / トロンボモジュリン / プロテインC / HMGB1 / PAMPs |
Research Abstract |
Endothelial thrombomodulin(TM) bounds DAMPs(Damage Associated Molecular Patterns);HMGB1,a representative DAMPs, histones. Moreover TM also bounds PAMPs(Pathogen Associated Molecular Patterns) ;lipopolysaccaride(LPS), a representative PAMPs, onto the lectin-like domain of the molecule and neutralizes their cytopathic activities, including proinflammatory and procoagulant activities. HMGB1 bound to TM, degraded by thrombin/TM complex and generated the N-terminus deleted HMGB1, named as des-HMGB1. Des-HMGB1 bound onto the receptors RAGE and TLR2-2, -4. However the binding affinity was weak compared to intact HMGB1, suggesting des-form of the molecule may configure a negative feedback loop among HMGB1 and its receptors regulating the diverse activities of HMGB1. Based on the findings, assay of des-HMGB1.may provide significant information in such morbid states including Disseminated Intravascular Coagulation(DIC), sepsis, systemic inflammatory response sybdrome(SIRS) and so on. Therefore we tried to establish specific assay method of des-HMGB1. We got specific monoclonal antibodies to react with the des-HMGB1. Using the monoclonal antibody, we established specific enzyme linked immune sorbent assay(ELISA). The ELISA successfully detected des-HMGB1 with 10% contamination of intact form. Des-HMGB1 was increased the serum from DIC, especially treated with recombinant TM. However the increased des-HMGB1 was decreased rapidly suggesting the rapid turn-over of the des-form. Moreover some patients showed no increased in des-HMGB1 even with recombinant TM treatment, suggesting of the presence or non-responder cases. Thus assessment of des-HMGB1 may be expected to provide a novel information in the DIC, SIRS, sepsis and so on with or without treatment.
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Report
(2 results)
Research Products
(13 results)
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[Journal Article] Role of high mobility group box chromosomal protein 1 in ischemia-reperfusion injury in the rat small intestine2012
Author(s)
Kojima M, Tanabe M, Shinoda M, Yamada S, Miyasho T, Suda K, Hibi T, Obara H, Itano O, Kawachi S, Kitajima M, Maruyama I, Kitagawa Y
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Journal Title
J Surg Res
Volume: 178(1)
Issue: 1
Pages: 466-71
DOI
Related Report
Peer Reviewed
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