2020 Fiscal Year Final Research Report

Mechanisms involved in pathogenesis of myocardial infarction by foam cell formation and inflammasome activation

Research Project

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Project/Area Number	18K09556
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57020:Oral pathobiological science-related
Research Institution	Kyushu Dental College
Principal Investigator	Tatsuji Nishihara 九州歯科大学, 歯学部, 特任教授 (80192251)
Co-Investigator(Kenkyū-buntansha)	有吉渉九州歯科大学, 歯学部, 教授 (40405551) 沖永敏則大阪歯科大学, 歯学部, 教授 (60582773)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	歯周病 / 心筋梗塞 / インフラマソーム / ピロトーシス / マクロファージ / 泡沫化
Outline of Final Research Achievements	Periodontopathic bacterium invasion induced secretion of interleukin (IL)-1β and expression of inflammasome-associated factors. Docosahexaenoic acid (DHA), an omega-3 fatty acid suppressed inflammasome-associated factors expression as well as IL-1β secretion by THP-1 cells in response to A. actinomycetemcomitans invasion. Moreover, we revealed that expression of adhesion molecules in endothelial cells and macrophages was upregulated by IL-17A. Furthermore, IL-17A stimulation resulted in expression of scavenger receptor in phorbol 12-myristate 13-acetate (PMA)-activated macrophages. Oil Red O also demonstrated that IL-17A enhanced foam cell formation by PMA-activated macrophages induced by oxidized low-density lipoprotein. These results indicated that IL-17A may be responsible for the pathogenesis of atherosclerosis by inducing the adhesion of leukocytes to vascular endothelium and foam cell formation.
Free Research Field	歯周病学
Academic Significance and Societal Importance of the Research Achievements	本研究事業では、歯周病細菌感染による炎症反応について、自然免疫の概念を見据えた研究を展開した。このような発想に立った感染症・炎症学研究は見られない。その結果、歯周病原性細菌の侵入によるインフラマソームを軸とした単球・マクロファージ系の炎症応答や炎症性サイトカインのアテローム性動脈硬化症発症の関与を示唆する成果を見出すことができた。ここで得られた成果により、歯周炎に関与する特異的な炎症性タンパクや病態形成に関わる分子メカニズムの一部が解明され、今後、歯周炎および歯周炎が関連する種々の全身疾患のリスクの低下に繋がる新たな予防・治療戦略の提案に寄与すると期待される。