G.R. Scott Budinger, M.D., Gokhan M Mutlu, M.D.
R01ES015024, R21ES025644, U01ES026718, R01ES013995
The diabetes drug metformin may reduce inflammation triggered by air pollution exposure, according to an NIEHS-funded study. The researchers reported that metformin prevented immune cells known as macrophages from releasing an inflammatory molecule called interleukin-6 (IL-6), which has been linked to heart attacks and strokes.
Mice were exposed to particulate matter air pollution and treated with or without metformin for three days. Treatment with metformin prevented the release of IL-6 in mice and reduced the susceptibility to arterial thrombosis, or blood clots, in the artery. The researchers also exposed both human and mouse lung cells to metformin treatment and found that it prevented the release of IL-6 following air pollution exposure.
Because several cellular processes in the mitochondria are required to release IL-6, the researchers tested the effects of air pollution on mice lacking certain mitochondrial proteins. Similar to mice treated with metformin, those lacking certain mitochondrial proteins were also protected against pollution-induced acceleration of arterial thrombosis, which suggested the involvement of mitochondria in this process.
Metformin is a safe and inexpensive drug used by more than 100 million diabetes patients worldwide. According to the authors, these findings suggested that metformin also has the potential to prevent inflammation caused by air pollution exposure.
Citation: Soberanes S, Misharin AV, Jairaman A, Morales-Nebreda L, McQuattie-Pimentel AC, Cho T, Hamanaka RB, Meliton AY, Walter JM, Chen CI, Chi M, Chiu S, Gonzalez-Gonzalez FJ, Antalek M, Adbala-Valencia H, Chiarella SE, Sun KA, Woods PS, Ghio AJ, Jain M, Perlman H, Ridge KM, Morimoto RI, Sznajder JI, Balch WE, Bhorade SM, Bharat A, Prakriya M, Chandel NS, Mutlu GM, Budinger GRS. 2018. Metformin targets mitochondrial electron transport to reduce air pollution-induced thrombosis. Cell Metab 29:1-13.