TLR3 activation and regulation in Sjogren's syndrome

Research Project

Project/Area Number	16K11500
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Pathobiological dentistry/Dental radiology
Research Institution	Nagasaki International University
Principal Investigator	Sohda Miwa 長崎国際大学, 薬学部, 講師 (20258528)
Co-Investigator(Kenkyū-buntansha)	梨田智子日本歯科大学, 新潟生命歯学部, 非常勤講師 (10133464)
Project Period (FY)	2016-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords	シェーグレン症候群 / 唾液分泌 / フラボノイド / TLR3
Outline of Final Research Achievements	Sjogren's syndrome is a systemic autoimmune disease characterized by dry eyes and a dry mouth. Previous studies have shown that Toll-like receptor 3 (TLR3) expression is enhanced in salivary glands of patients with Sjogren’s syndrome. In this study, we examined the effect of substances with TLR3 inhibitory effect on salivary secretion for finding the agent that relieves dry mouth symptoms. When administering Luteolin, which showed a high TLR3 inhibitory effect in A-253 cells derived from a human submandibular gland, to NOD mice of Sjogren's syndrome model mice, the salivary secretion rate stimulated by pilocarpine was significantly higher in the treated group compared with the control group. These results suggest that Luteolin could be a therapeutic agent for suppressing salivary gland dysfunction.
Academic Significance and Societal Importance of the Research Achievements	本疾患には、他の自己免疫疾患がない一次性と、他の自己免疫疾患（慢性関節リウマチ、全身性エリトマトーデス等）の罹患者が本疾患を併発する二次性に二分される。先行する自己免疫疾患の治療と並行して、発症前から唾液腺障害を予防するような使用法も想定できる。また、作用機序の検討から、本研究の成果は経年変化による唾液分泌量減少を抑制する効果を有するものとして、健康寿命の延伸への貢献も期待される。