2007 Fiscal Year Final Research Report Summary
Molecular mechanism for the regulation of septic shock by endogenous antimicrobial cathelicidin peptides
| Project/Area Number |
17590401
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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 |
Bacteriology (including Mycology)
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| Research Institution | Juntendo University |
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Principal Investigator |
NAGAOKA Isao Juntendo University, School of Medicine, Professor (60164399)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Taisuke Juntendo University, School of Medicine, Assistant Professor (40384135)
KUWAHARA-ARAI Kyoko (新井 京子) Juntendo University, School of Medicine, Assistant Professor (10167976)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Sepsis / Neutrophils / Apoptosis / Antimicrobial peptides / Cathelicidin / Defensins / Endotoxin shock / Lipopolvsaccharide |
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| Research Abstract |
Peptide antibiotics possess the potent antimicrobial activities against invading microorganisms and contribute to the innate host defense. An antibacterial cathelicidin, human LL-37 and hBDs (human B-defensins) not only exhibits potent bactericidal activities but also functions as a chemoattractant for immune cells including neutrophils. During bacterial infections including sepsis, the lifespan of neutrophils is regulated by various pathogen and host-derived substances. Here, to further evaluate the role of LL-37 and hBDs in innate immunity, we investigated their actions on neutrophil apoptosis.
Neutrophil apoptosis was assessed using human blood neutrophils based on the morphological changes. Of note, LL-37 and HBD-3 suppressed neutrophil apoptosis, accompanied with the phosphorylation of ERK-1/-2, expression of Bcl-XL (an anti-apoptotic protein) and inhibition of caspase 3 activity. Interestingly, LL-37- and hBD-3-induced suppression of neutrophil apoptosis was attenuated by the antagonists for formyl-peptide receptor-like 1 (FPRL1) and P2X7 nucleotide receptor, and a chemokine receptor CCR6, respectively.
Collectively, these observations indicate that LL-37 and hBD-3 can not only kill bacteria but also modulate (suppress) neutrophil apoptosis via the activation of FPRL1 and P2X7, and CCR6, respectively, in bacterial infections. Suppression of neutrophil apoptosis results in the prolongation of their life span and may be advantageous for host defense against bacterial invasion. However, the suppressed neutrophil apoptosis may causes the uncontrolled release of cytotoxic metabolites and pro-inflammatory substances (i.e. reactive oxygen species and proteases), which leads to the amplification of systemic inflammation, tissue injury and organ failure observed in sepsis.
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[Journal Article] Antibacterial cathelicidin peptide CAP 11 suppresses the anandamide production from lipopolysaccharide-stimulated mononuclear phagocytes2007
Author(s)
Murakami, T, Yomogida, S, Someya, A, Kuwahara-Arai, K, Tamura, H, Nagaoka, I
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Journal Title
FEBS Lett 581
Pages: 140-144
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Evaluation of the effects of antimicrobial cathelicidin peptide CAP11 on the production and release of anandamide and HMGB 1 in an endotoxin shock model. J Leukoc Biol Suppl : 272007
Author(s)
Murakami, T, Yomogida, S, Shibusawa, K, Okuda, D, Tamura, H, Nagaoka, I
Organizer
40th Annual Meeting of the Society for Leukocyte Biology
Place of Presentation
Massachusetts
Year and Date
20071000
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Suppressive effects of antibacterial cathelicidin peptide CAP 11 on the anandamide production from LPS-stimulated mononuclear phagocytes. J Leukoc Biol Suppl : 372006
Author(s)
Murakami, T, Okuda, D, Yomogida, S, Tamura, H, Nagaoka, I
Organizer
Joint conference of the Society for Leukocyte Biology 39th Annual Meeting and International Endotoxin and Innate Immunity Society 9th Biennial Meeting, San Antonio
Place of Presentation
Texas
Year and Date
20061100
Description
「研究成果報告書概要(欧文)」より
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