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

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 Exo or Exo, respectively. Macrophages were transfected with si-TREM-1 to explore the role of TREM-1 in Exo-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 Exo-induced M1 macrophage polarization and CS-induced lung injury. We isolated Exo and Exo successfully, and found that Exo promoted M1 macrophage polarization. Furthermore, we found that the promotion of Exo to M1 macrophage polarization was partly reversed by TREM-1 knockdown. The results of animal experiments showed that Exo administration aggravated CS-induced impairment in pulmonary function, lung injury and M1 macrophage polarization, which were partly rescued by TREM-1 silencing. Overall, Exo promoted M1 macrophage polarization by upregulating TREM-1 expression, thereby aggravating the development of COPD.