AT-RVD1 repairs mouse lung after cigarette smoke-induced emphysema via downregulation of oxidative stress by NRF2/KEAP1 pathway

Long-term exposure to cigarette smoke (CS) results in alveolar parenchyma destruction due to chronic inflammatory response and the imbalance between oxidants and antioxidants, and proteases and antiproteases. Emphysema is the main symptom of chronic obstructive pulmonary disease. Current treatment focuses on relieving respiratory symptoms, and inflammation resolution failure is an important pathophysiological element of the disease. Specialized pro-resolving mediators (SPMs) synthesized endogenously during resolution processes demonstrated beneficial effects in murine models of airway inflammation. Here, we aimed to test the SPM AT-RvD1 in a murine model of CS-induced emphysema. AT-RvD1 restored elastic fibers and lung morphology, with reduction in MMP-3, neutrophils, and myeloperoxidase activity and increases in macrophages and IL-10 levels. AT-RvD1 also decreased levels of oxidative stress markers and ROS via upregulation of the Nrf2/Keap1 pathway. Therefore, we suggest that AT-RvD1 causes pro-resolutive action in our murine model of CS-induced emphysema by upregulation of the Nrf2/Keap1 pathway. •Emphysema caused by long-term exposure to cigarette smoke in mice is repaired by AT-RvD1.•AT-RvD1 downregulated MMP3 and repaired elastic fibers in murine emphysema.•Cigarette smoke increased neutrophil-derived microparticles, and AT-RvD1 reversed this effect.•The pathway of Nrf2/Keap1 is modulated by AT-RvD1 favoring the expression of antioxidant enzymes.