New paradigm for innate immune regulatory mechanism and chronic inflammation mediated by ganglioside molecular species
| Project/Area Number |
17K19569
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathology, Infection/Immunology, and related fields
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 明身 東北医科薬科大学, 薬学部, 客員教授 (70134533)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | GM3ガングリオシド / 慢性炎症 / TLR4 / グロボシド / 糖尿病性腎症 / 自然免疫 / ガングリオシド / GM3 / メタボリックシンドローム / ガングリオシドGM3 |
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| Outline of Final Research Achievements |
The aim of this project is the elucidation of molecular mechanisms involved in the vicious cycle of chronic inflammation state induced by GM3 ganglioside-molecular species, and the examination of potential application of this evidence to the establishing of diagnosis and treatment for the vicious cycle.
90% of total gangliosides of human sera are GM3 molecular species. We have found a surprising evidence that very-long chain (VLCFA)-GM3 induce the secretion of inflammatory cytokines when monocytes or macrophages are stimulated by the TLR4 ligand, LPS or HMGB1, while long chain (LCFA)-GM3 suppress the secretion of inflammatory cytokines. Collectively, we propose a novel inflammation loop triggered by GM3 molecular species.
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| Academic Significance and Societal Importance of the Research Achievements |
TLR4に作用する炎症促進性GM3分子種および炎症抑制性GM3分子種が存在し、メタボリックシンドロームの進行に沿って、発現バランスが炎症促進性へシフトすることを見出した。これらのGM3分子種の生理活性は、セラミド構造中のアシル鎖の鎖長や飽和度、水酸化修飾によって制御されており、炎症促進性GM3分子種は極長鎖飽和アシル鎖をもつ分子種であり、一方、炎症抑制性GM3分子種は、長鎖または不飽和アシル鎖をもつ分子種であった。これらの知見から、患者血清中のGM3分子種の定量解析による慢性炎症状態の診断・評価法の開発や、炎症抑制性GM3投与による新たな慢性炎症制御法の開発が期待できる。
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Report
(3 results)
Research Products
(37 results)
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[Journal Article] Deficient ganglioside synthesis restores responsiveness to leptin and melanocortin signaling in obese KKAy mice.2018
Author(s)
Inamori K, Ito H, Tamura Y, Nitta T, Yang X, Nihei W, Shishido F, Imazu S, Tsukita S, Yamada T, Katagiri H, Inokuchi J
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Journal Title
Journal of Lipid Research
Volume: 59
Issue: 8
Pages: 1472-1481
DOI
Related Report
Peer Reviewed
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[Presentation] NPC1L1-dependent intestinal cholesterol absorption requires ganglioside GM3 in membrane microdomains.2018
Author(s)
Wataru Nihei, Masakazu Nagafuku, Hirotaka Hayamizu, Yuta Odagiri, Yumi, Tamura, Yui Kikuchi, Lucas Veillon, Hirotaka Kanoh, Kei-ichiro Inamori, Kenta Arai, Kazuya Kabayama, Koichi Fukase, Jin-ichi Inokuchi.
Organizer
10th 2018 Asian Community of Glycoscience and Glycotechnology Conference.
Related Report
Int'l Joint Research / Invited
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