Analysis of immune regulation by Angptls through immunoglobulin-like receptors

Research Project

Project/Area Number	25460595
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Immunology
Research Institution	University of the Ryukyus
Principal Investigator	UMIKAWA MASATO 琉球大学, 医学(系)研究科(研究院), 准教授 (00325838)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	Angptl2 / マクロファージ / 炎症 / 腹腔マクロファージ / アンギオポエチン様蛋白質 / 抑制性免疫グロブリン様受容体 / 免疫担当細胞
Outline of Final Research Achievements	We demonstrated that Angptl2 inhibits differentiation and promotes ex vivo expansion of Hematopoietic stem cells via immunoglobulin like receptors. Although recent studies implicate Angptl2 in chronic inflammation, the mechanisms of inflammation caused by Angptl2 remain unclear. In this study, we showed that Angptl2 directly activates resident murine peritoneal monocytes and macrophages and induces a drastic upregulation of the transcription of several inflammatory genes including nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, and several proinflammatory cytokine genes such as interleukin (IL)-1β, IL-6, TNFα, and CSF2. These results demonstrate a novel role for Angptl2 in inflammation via the direct activation of peritoneal monocytes and macrophages.