In vivo and in vitro Models of PM2.5 Induced COPD: Focus on the Role of RTA-408

Yibing Niu,1,2 Ling Zhang,3 Sumin Guo,4 Shucai Wu1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Huabei Petroleum Administration Bureau General Hospital, Renqiu, Hebei, People’s Republic of China; 3Department of Respiratory, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Oncology, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shucai Wu, Department of Internal Medicine, Hebei Medical University, 361 Zhongshan East Road, Chang’an District, Shijiazhuang, Hebei, 050017, People’s Republic of China, Tel/Fax +8618232155713, Email [email protected]: Inflammation and oxidative stress are important factors in the pathogenesis of Chronic obstructive pulmonary disease (COPD). Current treatments for COPD focus on improving symptoms caused by inflammation rather than curing the disease, therefore, emerging research focusing on upstream pathways may help develop effective treatments. Epidemiological investigations have shown that exposure to fine particulate matter (PM2.5) can cause lung inflammation and oxidative stress through nuclear factor NF-E2-associated factor (Nrf2) pathway, leading to COPD. Nrf2 is an important transcription factor regulating anti-inflammatory and antioxidant stress, and its abnormal expression level or changes in transcriptional activity are related to the occurrence and development of COPD. Omaviloxone - RTA-408, a synthetic oleanane triterpene that acts as an Nrf2 activator, RTA-408 may play an important role in COPD.Purpose: In this study, PM2.5 was used to establish HBE cell model in vitro and rat model in vivo to simulate COPD, and the effect of Nrf2 activator RTA-408 on PM2.5-induced COPD model and its mechanism were investigated.Patients and Methods: The HBE cell model in vitro and rat model in vivo were established to simulate COPD, and the effect of RTA-408 on COPD was detected by various experimental methods.Results: The results showed that RTA-408 could activate Nrf2 both in vivo and in vitro. By activating Nrf2/HO-1 pathway, RTA-408 inhibits NF-κB and IFN-γ pathways, alleviates inflammation and oxidative stress of HBE cells in COPD model rats and PM2.5 exposed cells, and plays a therapeutic role in reversing cell damage and delaying disease progression in COPD. In addition, in vitro experiments, silencing Nrf2 eliminated the protective effect of RTA-408 on COPD cell models, which also confirmed the role of RTA-408.Conclusion: We conclude that RTA-408 is well worth considering as a new strategy for the treatment of COPD, and may also have a positive preventive effect.Keywords: chronic obstructive pulmonary disease, inflammation, oxidative stress, Nrf2, RTA-408