Cigarette smoke extract-treated airway epithelial cells-derived exosomes promote M1 macrophage polarization in chronic obstructive pulmonary disease.

• TREM-1 expression was increased in ExoCSE compared to ExoPBS. • ExoCSE promoted M1 macrophage polarization by upregulating TREM-1 expression. • ExoCSE aggravated the CS-induced lung injury in COPD mice. Chronic obstructive pulmonary disease (COPD) is a persistent respiratory disorder that is primarily caused by exposure to cigarette smoke (CS). Exosomes have emerged as crucial mediators of intercellular communication, but their role in CS-induced COPD is not fully understood. Here, we investigated whether exosomes derived from cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs) promote M1 macrophage polarization by upregulating triggering receptor expressed on myeloid cells-1 (TREM-1) expression during COPD pathogenesis. The exosomes isolated from PBS- or CSE-treated MAECs were named as ExoPBS or ExoCSE, respectively. Macrophages were transfected with si-TREM-1 to explore the role of TREM-1 in ExoCSE-induced M1 macrophage polarization. The lentivirus expressing shTREM-1 was injected into COPD model mice by intranasal instillation, which was carried out to explore the in vivo role of TREM-1 in ExoCSE-induced M1 macrophage polarization and CS-induced lung injury. We isolated ExoPBS and ExoCSE successfully, and found that ExoCSE promoted M1 macrophage polarization. Furthermore, we found that the promotion of ExoCSE to M1 macrophage polarization was partly reversed by TREM-1 knockdown. The results of animal experiments showed that ExoCSE administration aggravated CS-induced impairment in pulmonary function, lung injury and M1 macrophage polarization, which were partly rescued by TREM-1 silencing. Overall, ExoCSE promoted M1 macrophage polarization by upregulating TREM-1 expression, thereby aggravating the development of COPD. [ABSTRACT FROM AUTHOR]