炎症体
化学
髓过氧化物酶
结肠炎
一氧化氮
谷胱甘肽
生物化学
炎症
半胱氨酸蛋白酶1
一氧化氮合酶
药理学
富马酸二甲酯
线粒体ROS
细胞凋亡
分子生物学
免疫学
酶
生物
有机化学
受体
多发性硬化
作者
Xiuting Liu,Wei Zhou,Xin Zhang,Ping Lü,Qianming Du,Lei Tao,Yang Ding,Yajing Wang,Rong Hu
标识
DOI:10.1016/j.bcp.2016.05.002
摘要
In the present study, we examined the effects of dimethyl fumarate (DMF) on dextran sulfate sodium (DSS)-induced murine colitis, an animal model which mimics human IBD. Oral administration of DMF dose-dependently attenuated body weight loss, colon length shortening and colonic pathological damage including decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities in DSS-treated mice. Increased glutathione (GSH) induced by DMF demonstrated its potential antioxidant capacity. In addition, Nrf2 and its downstream genes were markedly activated by DMF. Furthermore, protein and mRNA levels of pro-inflammatory cytokines, including IL-1β, TNF-α and IL-6 were markedly suppressed by DMF. At the same time, decreased activation of caspase-1 was detected in DMF-treated mice, indicating that the NLRP3 inflammasome activation was suppressed. The in vitro study verified a negative regulation of DMF and its intestinal metabolite on NLRP3 inflammasome. Moreover, the inhibitory effect was found to be mostly dependent on Nrf2 which decreased mitochondrial ROS (mROS) generation and mitochondrial DNA (mtDNA) release. Taken together, our results demonstrated the ability of DMF to inhibit NLRP3 inflammasome activation and its potential use in the treatment of NLRP3-associated diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI