Abstract
Exposure to particulate matter has been associated with diseases of the respiratory and cardiovascular systems. Owing to the dense vasculature of the kidney, it has also been identified as a PM2.5 target organ. A potential contributor to PM2.5-mediated damage may be the promotion of inflammation. The essential oil 2-undecanone (2-methyl nonyl ketone) is an H. cordata isolate, and it has been shown to possess diverse pharmacologic effects, including anti-inflammatory properties. In this study we explored the ability of 2-undecanone to protect against PM2.5-induced kidney inflammation and the exact mechanisms in this process. We found that PM2.5 elevated the levels of certain inflammatory cytokines in BALB/c mice and in HEK 293 cells. Supplementation with 2-undecanone attenuated this PM2.5-induced inflammatory injury. Interestingly, in HEK 293 cells, the PM2.5-associated inflammation was aggravated by the mitophagy inhibitor Medivi-1, while it was attenuated by rapamycin, indicating that the mechanism of 2-undecanone-mediated inhibition of inflammation may relate to mitophagy. Meanwhile, 2-undecanone induces mitophagy in HEK 293 cells by suppressing Akt1-mTOR signaling. These results indicate that PM2.5 can induce kidney inflammation, and mitophagy induced by 2-undecanone may play a protective role against this renal inflammation.