Roles of NETs and alarmins in the pathogenesis of sepsis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460538
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Juntendo University
• Principal Investigator: NAGAOKA ISAO 順天堂大学, 医学(系)研究科(研究院), 教授 (60164399)
• Co-Investigator(Renkei-kenkyūsha): TABE Yoko 順天堂大学, 医学部, 教授 (70306968)
• Research Collaborator: HU Zhongshuang
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: NETs / alarmin / 敗血症 / 抗菌ペプチド / サイトカイン / DAMPs / 細胞死

Outline of Final Research Achievements

LL-37 is an alarmin with antimicrobial activity. In addition to its broad spectrum of antimicrobial activities, LL-37 can modulate inflammatory reactions. In the present study, we elucidated the mechanism for the action of LL-37 on the septic mice, focusing on the release of neutrophil extracellular traps (NETs). The results indicated that the administration of LL-37 suppressed the increase of DAMPs (such as histone-DNA complex and HMGB1) as well as IL-1β, TNF-α and the bacterial burdens. Notably, LL-37 increased the level of NETs. In addition, we confirmed that LL-37 induces the release of NETs from neutrophils, and NETs possess the bactericidal activity. Together, these observations suggest that LL-37 improves the survival of septic mice by suppressing the inflammatory responses as evidenced by the inhibition of the increase of cytokines and DAMPs (host cell death), and the bacterial growth via the release of NETs with the bactericidal activity.

Free Research Field

生体防御学