ADIPOSE-DERIVED STEM CELLS-DERIVED EXOSOMES ATTENUATE CIGARETTE SMOKE-INDUCED LUNG INFLAMMATION AND INJURY VIA DECREASING ALVEOLAR MACROPHAGES PYROPTOSIS

TYPE: Abstract TOPIC: Obstructive Lung Diseases PURPOSE: To investigate the protective roles of adipose-derived stem cells-derived exosomes (ADSCs-Exo) in cigarette smoke (CS)-induced COPD and explore the underlying mechanism by discovering the effects of ADSCs-Exo on alveolar macrophages (AMs) pyroptosis. METHODS: ADSCs were isolated from human adipose tissues, and then ADSCs-Exo were isolated. 24 8-week-old male C57/BL6 mice were exposed to CS for 4 weeks, followed by intratracheal administration of ADSCs-Exo or PBS. MH-S cells, derived from mouse AMs, were stimulated by 2% CS extract for 24 hours, followed by ADSCs-Exo or PBS treatment. Pulmonary inflammation was analyzed by detecting pro-inflammatory cells and mediators in the bronchoalveolar lavage fluid. Lung histology was assessed by HE staining. Mucus production was determined by PAS staining. The profile of AMs pyroptosis was evaluated by detecting the levels of pyroptosis-indicated proteins. The inflammatory response in AMs and the phagocytic activity of AMs were investigated. RESULTS: In mice with CS-induced COPD, the levels of pro-inflammatory cells and mediators were significantly were increased, mucus production was markedly increased and lung architecture was obviously disrupted. AMs pyroptosis was elevated and AMs phagocytosis was inhibited. However, the administration of ADSCs-Exo greatly reversed these alterations caused by CS exposure. Consistently, in MH-S cells with CS extract-induced COPD, the cellular inflammatory response was elevated, the pyroptotic activity was upregulated while the phagocytosis was decreased. Nonetheless, these abnormalities were remarkably alleviated by the treatment of ADSCs-Exo. CONCLUSIONS: ADSCs-Exo significantly attenuates CS-induced airway mucus overproduction, lung inflammation and injury by inhibiting AMs pyroptosis. CLINICAL IMPLICATIONS: ADSCs-Exo may be a promising cell-free therapeutic candidate for COPD. DISCLOSURE: Nothing to declare. KEYWORD: Chronic obstructive pulmonary disease