The analysis of inflammasome activation in extracellular histones

• Project/Area Number: 26293387
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Osaka Institute of Technology
• Principal Investigator: Kawahara Ko-ihi 大阪工業大学, 工学部, 教授 (10381170)
• Co-Investigator(Kenkyū-buntansha): 丸山 征郎 鹿児島大学, 医歯(薬)学総合研究科, 教授 (20082282) ; 伊藤 隆史 鹿児島大学, 医歯(薬)学総合研究科, 講師 (20381171) ; 森元 陽子 鹿児島大学, 医学部・歯学部附属病院, 助教 (30437967) ; 三浦 直樹 鹿児島大学, 獣医学部, 准教授 (80508036) ; 中島 利博 東京医科大学, 医学部, 教授 (90260752)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: 敗血症 / インフラマソーム / ヒストン / オートファジー / DAMPs

Outline of Final Research Achievements

Recently, extracellular histones are damage-associated molecular patterns (DAMPs), which is released by necrotic cells. However, extracellular histones remain unclear as DAMPs. In this study, we focused whether extracellular histones activate inflammasome (IL-1β release) in macrophage cell lines, which are ASC in the presence or absence. Therefore, histones induced IL-1βin macrophage cell-lines in the presence or absence ASC, suggesting that sepsis might enhance in extracellular histones.

Research Products

• [Journal Article] “DAMP and DIC: The role of extracellular DNA and DNA-binding proteins in the pathogenesis of DIC” (2016)
  • Author(s): Liaw P, Ito T, Iba T, Thachil J, Zeerleder S
  • Journal Title: Blood Rev. Volume: 30
  • Peer Reviewed
• [Journal Article] A natural therapeutic approach for the treatment of periodontitis by MK615. (2015)
  • Author(s): Yoko Morimoto-Yamashita, Yoshiko Kawakami, Syoko Tatsuyama, Keiko Miyashita, Makiko Emoto, Kiyoshi Kikuchi, Ko-ichi Kawahara, Masayuki Tokuda
  • Journal Title: Medical Hypotheses Volume: 85 Issue: 5 Pages: 618-621
  • DOI: 10.1016/j.mehy.2015.07.028
  • Peer Reviewed / Open Access
• [Journal Article] GM2 gangliosidosis variant 0 (Sandhoff disease) in a mixed-breed dog. (2015)
  • Author(s): Kohyama, M., Yabuki, A., Kawasaki, Y., Kawaguchi, H., Miura, N., Kitano, Y., Onitsuka, T., Rahmann, MM., Miyoshi, N., Yamato, O.
  • Journal Title: J Am Anim Hosp Assoc Volume: 51
  • Peer Reviewed
• [Journal Article] Diagnostic imaging of intra-abdominal cyst in heifer using the computed tomography (2015)
  • Author(s): Otomaru, K., Fujikawa, T., Saito, Y., Ando, T., Obi, T., Miura, N., Kubota, C.
  • Journal Title: Journal of Veterinary Medical Science Volume: 77 Issue: 9 Pages: 1191-1193
  • DOI: 10.1292/jvms.15-0153
  • NAID: 130005100727
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1β. (2015)
  • Author(s): Fujita H, Yagishita N, Aratani S, Saito-Fujita T, Morota S, Yamano Y, Hansson MJ, Inazu M, Kokuba H, Sudo K, Sato E, Kawahara K, Nakajima F, Hasegawa D, Higuchi I, Sato T, Araya N, Usui C, Nishioka K, Nakatani Y, Maruyama I, Usui M, Hara N, Uchino H, Elmer E, Nishioka K, Nakajima T.
  • Journal Title: EMBO J. Volume: 34 Issue: 8 Pages: 1042-55
  • DOI: 10.15252/embj.201489897
  • Peer Reviewed / Open Access
• [Journal Article] Cleavage of host cytokeratin-6 by lysine-specific gingipain induces gingival inflammation in periodontitis patients. (2015)
  • Author(s): Tancharoen S, Matsuyama T, Kawahara K, Tanaka K, Lee LJ, Machigashira M, Noguchi K, Ito T, Imamura T, Potempa J, Kikuchi K,Maruyama I.
  • Journal Title: PLoS One. Volume: 10 Issue: 2 Pages: e0117775-e0117775
  • DOI: 10.1371/journal.pone.0117775
  • Peer Reviewed / Open Access
• [Journal Article] HMGB1 promotes the development of pulmonary arterial hypertension in rats. (2014)
  • Author(s): Sadamura-Takenaka Y, Ito T, Noma S, Oyama Y, Yamada S, Kawahara K, Inoue H, Maruyama I.
  • Journal Title: PLoS One. Volume: 9 Issue: 7 Pages: e102482-e102482
  • DOI: 10.1371/journal.pone.0102482
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 細胞外ヒストンにおけるIL-1β放出機構の解明 (2015)
  • Author(s): 大池加恵、勝野涼太、藤本靖真、安田 哲 丸山征郎、川原幸一
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] 細胞外ヒストンによる炎症性サイトカインIL-1β放出機構の解明 (2015)
  • Author(s): 大池加恵、勝野涼太、藤本靖真、安田哲、丸山征郎、菊池清志、川原幸一
  • Organizer: 西日本生理学会
  • Place of Presentation: 久留米
  • Year and Date: 2015-10-09