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The possibility that suppression of NETosis contributes to improvement of SLE

Research Project

Project/Area Number 26461490
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionKitasato University

Principal Investigator

Takeuchi Yasuo  北里大学, 医学部, 教授 (60286359)

Co-Investigator(Kenkyū-buntansha) 竹内 恵美子  北里大学, 医学部, 講師 (00406935)
大津 真  東京大学, 医科学研究所, 准教授 (30361330)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords全身性エリテマトーデス / 好中球 / NETosis / プログラム細胞死 / 好中球活性酸素 / p40phox / siRNA / 好中球Netosis / NADPH酵素複合体 / 自己抗原提示 / 活性酸素
Outline of Final Research Achievements

Neutrophils contribute to antimicrobial defense by releasing nuclear chromatin together with granule proteins to form an extra cellular mesh which binds and kills bacteria.This formation, called neutrophil extracellular traps (NETs), considered to be implicated in anti-nucleotide antibody (ANA) positive Systemic Lupus Erythematosus (SLE).Activated neutrophils has been shown to involve the NADPH oxidase (NOX2) mediated production of reactive oxygen species (ROS), leading to disintegration of the nuclear envelope and result in induction of NETosis. In this study, we investigated the causal relation between NOX2 dependent/independent ROS production and extracellular DNA releasing. It was observed that the deletion of NOX2 in neutrophils accelerated mitochondrial ROS production with lps stimulation and released oxidative damaged DNA. Addition of anti-oxDNA antibodies induced more NETosis in vitro assay. Therefore, further analysis of the pathogenesis of anti-oxDNA Ab is needed.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (2 results)

All 2017

All Presentation (2 results)

  • [Presentation] .LupusモデルマウスBXSBを用いた好中球NETosisの新たな定量と定性解析2017

    • Author(s)
      竹内恵美子、森澤慎、竹内康雄
    • Organizer
      第45回 日本臨床免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] .Quantitative analysis of Neutrophil extracellular traps (NETs) in lupus prone mouse using novel methods2017

    • Author(s)
      Shin Morisawa、Emiko Takeuchi, Yauso Takeuchi
    • Organizer
      The 46th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2017 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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