Elucidation of the novel molecular mechanisms of proinflammatory cytokine production regulated by metabolism-related molecules

• Project/Area Number: 15K19077
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Wakayama Medical University
• Principal Investigator: Sasaki Izumi 和歌山県立医科大学, 先端医学研究所, 助教 (80611037)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: コレラ毒素

Outline of Final Research Achievements

Cholera toxin (CT) is strong immune adjuvant, which can induce Th17 responses. However, the mechanisms remain unclear. We have found that CT plus lipopolysaccharides (LPS) can synergistically induce IL-1 beta production. Our aim is to elucidate the mechanism of this IL-1 beta production. Integrated analysis of transcriptome and metabolome revealed that CT and CT plus LPS activated arginine metabolic pathway and histamine synthetic pathway, respectively. In this research, we have showed that the physiological role of these metabolic pathway in CT plus LPS-induced IL-1 beta production.

Research Products

• [Journal Article] Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. (2016)
  • Author(s): Ohta T, Sugiyama M, Hemmi H, Yamazaki C, Okura S, Sasaki I, Fukuda Y, Orimo T, Ishii KJ, Hoshino K, Ginhoux F, Kaisho T.
  • Journal Title: Scientific Reports Volume: 162 Issue: 1 Pages: 23505-23505
  • DOI: 10.1038/srep23505
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells. (2015)
  • Author(s): H. Sasaki, D. Kurotaki, N. Osato, H. Sato, I. Sasaki, S. Koizumi, H. Wang, C. Kaneda, A. Nishiyama, T. Kaisho, H. Aburatani, H. C. Morse III, K. Ozato, T. Tamura.
  • Journal Title: Blood Volume: 125(2) Issue: 2 Pages: 358-369
  • DOI: 10.1182/blood-2014-02-557983
  • Peer Reviewed / Open Access
• [Presentation] Spi-Bは圧負荷による心不全の病態形成において炎症と繊維化を抑制して保護的に機能する (2017)
  • Author(s): 木村章彦、石田裕子、野坂みずほ、佐々木泉、山本寛貴、國中由美、加藤喬、福田有里、改正恒康、近藤稔和
  • Organizer: 第38回 日本炎症・再生医学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2017-07-18
• [Presentation] Metabolic basis for cholera toxin-induced IL-1beta production in synergy with lipopolysaccharides (2016)
  • Author(s): SASAKI Izumi, FUKUDA Shinji, ORIMO Takashi, HEMMI Hiroaki, FUKUDA Yuri, OHTA Tomokazu & KAISHO Tsuneyasu
  • Organizer: 第45回 日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター、ラグナガーデンホテル
  • Year and Date: 2016-12-05
• [Presentation] Crosstalk between XCR1-expressing dendritic cells and intestinal T cells keeps intestinal homeostasis through the XCR1-XCL1 chemokine axis (2016)
  • Author(s): OHTA Tomokazu, HEMMI Hiroaki, FUKUDA Yuri, SASAKI Izumi, ORIMO Takashi & KAISHO Tsuneyasu
  • Organizer: 第45回 日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター、ラグナガーデンホテル
  • Year and Date: 2016-12-05
• [Presentation] Role of the polyamine pathway in Cholera toxin-induced production of proinflammatory cytokines (2015)
  • Author(s): ORIMO Takashi, SASAKI Izumi, FUKUDA Shinji, HEMMI Hiroaki, FUKUDA Yuri, KAISHO Tsuneyasu
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18
• [Remarks] 和歌山県立医科大学 先端医学研究所 生体調節機構研究部
  • URL: http://www.wakayama-med.ac.jp/med/seitai/index.php
• [Remarks] 和歌山県立医科大学 先端医学研究所 生体調節機構研究部
  • URL: http://www.wakayama-med.ac.jp/med/seitai/index.php