2-Undecanone Protects against Fine Particle-Induced Kidney Inflammation via Inducing Mitophagy

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 PM_2.5 target organ. A potential contributor to PM_2.5-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 PM_2.5-induced kidney inflammation and the exact mechanisms in this process. We found that PM_2.5 elevated the levels of certain inflammatory cytokines in BALB/c mice and in HEK 293 cells. Supplementation with 2-undecanone attenuated this PM_2.5-induced inflammatory injury. Interestingly, in HEK 293 cells, the PM_2.5-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 PM_2.5 can induce kidney inflammation, and mitophagy induced by 2-undecanone may play a protective role against this renal inflammation.