Inhibitory effects of supramolecular polyrotaxanes in inflammatory signaling and the application to the treatment of fulminant hepatitis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19904
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Tamura Atsushi 東京医科歯科大学, 生体材料工学研究所, 准教授 (80631150)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: ポリロタキサン / シクロデキストリン / コレステロール / 炎症 / Toll-like receptor

Outline of Final Research Achievements

It is reported that cholesterol and its metabolites are involved in the inflammatory responses, and the cross-talk between sterols and immunological system has received increasing attention. In this study, the effects of β-cyclodextrin-threaded acid-degradable polyrotaxanes, which directly interact with intracellular cholesterols, on the inflammatory responses were explored. When the polyrotaxane-treated cells were stimulated with lipopolysaccharide, the inflammatory responses were remarkably inhibited accompanied by the reduction of intracellular free cholesterol content. Additionally, the polyrotaxanes suppressed the inflammatory responses in a mouse model of lipopolysaccharide-induced fulminant hepatitis. According to these results, it is expected that the polyrotaxanes would be applied for the treatment of various inflammatory diseases.

Free Research Field

生体材料学

Academic Significance and Societal Importance of the Research Achievements

これまでにβ-シクロデキストリン含有ポリロタキサンによるコレステロール低下作用はニーマンピック病C型などのコレステロールの輸送障害が生じる疾患に対して有効であることが明らかとなっているが、本研究ではポリロタキサンによるコレステロールへの作用が細胞の炎症応答を抑制するという新たな知見を得た。また、急性炎症を引き起こしたマウスモデルでもポリロタキサンによる炎症応答抑制作用が確められた。詳細な作用機序についてはさらなる研究が必要であるが、炎症が原因となる疾患の治療に役立てることができると期待される。