2‐undecanone protects against fine particles‐induced heart inflammation via modulating Nrf2/HO‐1 and NF‐κB pathways

炎症 NF-κB 氧化应激 信号转导 抗氧化剂 化学 NFKB1型 细胞生物学 药理学 免疫学 生物 转录因子 生物化学 基因
作者
Yuhang Jiao,Shaopeng Wang,Liping Jiang,Xiance Sun,Jing Li,Xiaofang Liu,Xiaofeng Yao,Cong Zhang,Ningning Wang,Haoyuan Deng,Guang Yang
出处
期刊:Environmental Toxicology [Wiley]
卷期号:37 (7): 1642-1652 被引量:13
标识
DOI:10.1002/tox.23513
摘要

Exposure to air pollution has been closely associated with some cardiovascular disease. One of the mechanisms of PM2.5 -mediated heart injury may be to promote inflammation. We aim to investigate whether the main extract of Houttuynia cordata, 2-undecanone, can prevent the inflammation caused by PM2.5 , and to reveal the underlying mechanisms. The results showed that PM2.5 increased the expression of certain inflammatory cytokines, and caused oxidative damage in BALB/c mice and H9C2 cells. Supplementation with 2-undecanone attenuated this PM2.5 -induced inflammatory injury and oxidative damage. Further, we elucidated that the protective effect of 2-undecanone may be associated with NF-κB and Nrf2/HO-1 pathways. The NF-κB pathway was distinctly activated after treated by PM2.5 , which can be blocked by 2-undecanone, accompanied by increasing Nrf2 and HO-1 levels. To figure out the relationship between NF-κB and Nrf2/HO-1 pathways, we knocked down Nrf2 gene. NF-κB pathway proteins and downstream inflammatory cytokines were significantly increased after treatment with PM2.5 , while 2-undecanone could decrease expression of these proteins. In conclusion, it is possible that 2-undecanone can induce the expression of the antioxidant enzyme HO-1 by activating Nrf2, thereby reducing NF-κB pathway and inflammatory damage of mouse myocardium caused by PM2.5 exposure.
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