|Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|Outline of Final Research Achievements
The aim of this study was elucidating the intracellular iron dynamics in intestinal macrophages under inflammatory conditions and unveiling the contribution of disrupted iron regulatory mechanism in intestinal macrophages to the pathophysiology of IBD. Using DSS induced acute colitis mouse model, we demonstrated intestinal inflammation increased the expression of ferritin in intestinal macrophages which was followed by the increased expression of ferroportin-1, an iron exporter. In the in vitro experiments using bone marrow-derived murine macrophages, we found decreased IL-12p40 production in Ferroportin1 knock down macrophages compared to the controls after stimulation with LPS. Suppressing ferroportin1 might affect the expression of Nrf2, a transcriptional factor which regulates ferroportin-1 expression and was recently reported to directly suppress the production of proinflammatory cytokines in macrophages and result in the decreased Il12b expression.