IL-1beta production depending on size of insoluble material generated in vivo

• Project/Area Number: 25670192
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Kyoto University
• Principal Investigator: INABA Kayo 京都大学, 生命科学研究科, 教授 (00115792)
• Co-Investigator(Kenkyū-buntansha): TAKAHARA Kazuhiko 京都大学, 大学院生命科学研究科, 講師 (90301233)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 微細粒子 / IL-1β / アミロイド β / 炎症 / 凝集体 / マイクログリア / アミロイド-b / 原子間力顕微鏡 / IL-1beta / アミロイド-beta / 尿酸結晶

Outline of Final Research Achievements

Small particles/aggregates are known to provoke inflammatory response of macrophages (Mφ). In this study, latex beads (LxB) of 1000 nm and 20 nm, but not 100 nm in diameter, were shown to induce IL-1β production of Mφ-like microglia in the brain. Although aggregates of amyloid β (Aβ) are believed as causative agent of Alzheimer disease, only nano-sized Aβ oligomers, but not large Aβ fibril, stimulated IL-1β production of MG. In addition, the induction of IL-1β by nano-sized Aβ oligomers was dependent on reactive oxygen species (ROS) and protease cathepsin B. These results suggest that size/form of small particles/aggregates affects IL-1β production of MG.

Research Products

• [Journal Article] Amyloid β oligomers induce interleukin-1β production in primary microglia in a cathepsin B- and reactive oxygen species-dependent manner (2015)
  • Author(s): Taneo, J., Adachi, T., Yoshida, A., Takeyasu, K.,Takahara, K. and Inaba, K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 458 Pages: 561-567
  • DOI: 10.1016/j.bbrc.2015.02.006
  • NAID: 120005575184
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Functional Evaluation of Activation-dependent Alteration of Sialoglycans in T Cells (2014)
  • Author(s): Naito-Matsui Y, Takada S, Kano Y, Iyoda T, Sugai M, Shimizu A, Inaba K, Nitschke L, Tsubata T, Oka S, Kozutsumi Y, and Takematsu H.
  • Journal Title: J.Bio.Chem. Volume: 289 Pages: 1564-1579
  • DOI: 10.1074/jbc.m113.523753
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes (2014)
  • Author(s): Tomura M, Hata A, Matsuoka S, Shand FH, Nakanishi Y, Ikebuchi R, Ueha S, Tsutsui H, Inaba K, Matsushima K, Miyawaki A, Kabashima K, Watanabe T, Kanagawa O.
  • Journal Title: Scientific Reports Volume: 4 Pages: 1-11
  • DOI: 10.1038/srep06030
  • NAID: 120005749847
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Particle size of latex beads dictates IL-1β production mechanism (2013)
  • Author(s): Adachi, T., Takahara, K., Taneo, J., Uchiyama, Y. and Inaba, K.
  • Journal Title: Plos One Volume: 8
  • DOI: 10.1371/journal.pone.0068499
  • NAID: 120005307064
  • Peer Reviewed
• [Presentation] Amyloid b oligomers, but not fibrils, induced IL-1b production by mouse microglia (2013)
  • Author(s): Takumi Adachi, Kazuhiko Takahara, Jun Taneo and Kayo Inaba
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉、幕張
• [Remarks] 京都大学生命科学研究科高次生命科学専攻体制統御学講座生体応答学分野
  • URL: http://zoo.zool.kyoto-u.ac.jp/imm/
• [Remarks] 京都大学生命科学研究科高次生命科学専攻生体応答学分野ホームページ
  • URL: http://zoo.zool.kyoto-u.ac.jp/imm/