Dual functions of extracellular histones in host defense: Detection, characterization, and the mode of action of antimicrobial and cytotoxic region within histone H3

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphology/Structure
• Research Institution: Toho University
• Principal Investigator: IWAMURO Shawichi 東邦大学, 理学部, 教授 (70221794)
• Co-Investigator(Kenkyū-buntansha): 小林 哲也 埼玉大学, 理工学研究科, 教授 (00195794) ; 菊山 榮 早稲田大学, 教育・総合科学学術院, 名誉教授 (20063638) ; 蓮沼 至 東邦大学, 理学部, 講師 (40434261) ; 岡田 令子 静岡大学, 理学部, 講師 (50386554) ; 中野 真樹 東邦大学, 理学部, 博士研究員 (20646195)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ヒストン / 生体防御ペプチド / 細胞膜透過ペプチド / 細胞毒性 / 抗微生物活性 / リュウキュウアカガエル

Outline of Final Research Achievements

Recent reports have demonstrated the existence of extracellular histones. Extracellular histones have been shown to explicitly display antimicrobial properties and are known to be the major mediators of death during sepsis. In this study, we investigated antimicrobial and cytotoxic effects and the mode of action of histone H3 on various bacterial, fungal, and mammalian cells and identified functional region(s) within histone H3. The following results were obtained: (1) histone H3 exhibits growth-inhibitory effects against gram-negative and -positive bacteria and fungi through cell membrane destruction; (2) histone H3 exhibits strong cytotoxic effects on normal, immortal, and tumor cell lines through cell membrane destruction, but a lower cell density is required for immortal and tumor cells than for normal cells; (3) antimicrobial and cytotoxic functions are derived from different regions within histone H3.

Free Research Field

分子生理学