Role of inflamasome in corneal inflammation

Research Project

Project/Area Number	17K11468
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Ophthalmology
Research Institution	Nihon University
Principal Investigator	SAKIMOTO Tohru 日本大学, 医学部, 准教授 (20465272)
Co-Investigator(Kenkyū-buntansha)	山上聡日本大学, 医学部, 教授 (10220245)
Project Period (FY)	2017-04-01 – 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 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	角膜 / 炎症 / インフラマソーム / 角膜炎症 / 細胞・組織 / 生体分子 / 蛋白質 / 発現制御 / 免疫学
Outline of Final Research Achievements	We evaluated the role of NLR family pyrin domain containing 3 (NLRP3)　inflammasome in sterile　corneal inflammation caused by lipopolysaccharide (LPS) or alkali burns in C57BL6 mice or NLRP3 KO (Nlrp3－/－) mice. Various molecules related to the NLRP3 inflammasome were upregulated in C57BL6 mice after both alkali burn injury and LPS treatment. After alkali burn injury, the corneal opacity grade was significantly reduced in Nlrp3－/－ mice compared with C57BL6 mice. In Nlrp3－/－ mice, Gr-1 immunoreactivity and MMP-9 mRNA expression in the corneal stroma were significantly reduced by both LPS treatment and alkali burn injury. Quantitative PCR and immunohistochemistry revealed that IL-1β and MMP-9 expression in the corneal stroma were down-regulated in Nlrp3－/－ mice with both alkali burn injury and LPS treatment. These findings suggest that the NLRP3 inflammasome has a proinflammatory effect in the cornea by recruiting neutrophils to sites of inflammation.
Academic Significance and Societal Importance of the Research Achievements	各領域の様々な慢性疾患や炎症性疾患での関与を指摘されているNLRP3インフラマソームが、無菌性角膜炎症において炎症促進に関与していることを初めて明らかにした。また、角膜におけるNLRP3は好中球依存性にIL-1β・MMP-9発現を誘導し、炎症促進に関与することを示した。これらのことから、角膜における無菌性炎症である周辺部角膜潰瘍などの非感染性角膜潰瘍の病態にNLRP3インフラマソームが関与する可能性を示した。