Resolvin E1 and its precursor 18R-HEPE restore mitochondrial function in inflammation.

ABSTRACT

Inflammatory disorders such as sepsis are a major cause of morbidity and mortality. Mitochondrial dysfunction is considered a key factor in the pathogenesis of severe inflammation. In the present study, we aimed to investigate the impact of arachidonic acid, omega-3 (n-3) fatty acids, and n-3-derived lipid mediators 18R-HEPE and resolvin (Rv) E1 on mitochondrial function in experimental inflammation. The results revealed that, in contrast to n-6 and n-3 fatty acids, both 18R-HEPE and RvE1 possess anti-inflammatory and anti-apoptotic properties. Both mediators are able to restore inflammation-induced mitochondrial dysfunction, which is characterized by a decrease in mitochondrial respiration and membrane potential, as well as an imbalance of mitochondrial fission and fusion. Furthermore, inhibition of mitochondrial fission by Mdivi-1 and Dynasore reduces levels of the pro-inflammatory cytokines IL-6 and IL-8. These results suggest a novel functional mechanism for the beneficial effects of RvE1 in inflammatory reactions.