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 Type	Multi-year Fund
Section	一般
Research Field	Collagenous pathology/Allergology
Research Institution	Kitasato 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.