PM2.5 Promotes Macrophage-Mediated Inflammatory Response Through Airway Epithelial Cell-Derived Exosomal miR-155-5p

Abstract

Hui Xu,1,2 Xin Li,1 Kai Liu,1 Ping Huang,1 Xiao-Ju Liu1,2 1The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2The First Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Xiao-Ju Liu, Email [email protected]: Airway epithelial cells (AECs) and alveolar macrophages are involved in airway inflammation. The direct effects of atmospheric fine-particulate-matter (PM2.5) on airway cells, such as AECs and alveolar macrophages, have been widely investigated, but the effect of cell-cell interaction on inflammatory response remains unclear. Exosomes play a crucial role in intercellular communication. However, the cellular interaction of exosomes in PM2.5-induced airway inflammation is unclear.Methods: The PM2.5-induced human bronchial epithelial (BEAS-2B) cells and phorbol 12-myristate 13-acetate-induced macrophages (M&phis;) were co-cultured and then the expression of IL-6, IL-1β, TNF-α and miRNA-155-5p were detected. Exosomes from PM2.5-exposed BEAS-2B cells were then co-cultured with M&phis; to detect the expression of miR-155-5p and inflammatory cytokines, as well as cytokine signaling inhibitor-1 (SOCS1)/NFκB, and to detect the effect of the exosome inhibitor GW4869.Results: After the co-culture of PM2.5-induced BEAS-2B cells and M&phis;, the expression of M&phis;-derived IL-6, IL-1β, and TNF-α, as well as miRNA-155-5p were upregulated. The expression of miRNA-155-5p was upregulated in BEAS-2B and BEAS-2B cell-derived exosomes after exposure to PM2.5. Furthermore, co-culturing exosomes derived from PM2.5-exposed BEAS-2B cells with M&phis;, upregulated miR-155-5p and inflammatory cytokines, decreased cytokine signaling inhibitor-1 (SOCS1) expression, and activated NF-κB. In addition, adding exosome inhibitor GW4869 to PM2.5-interfered BEAS-2B cells co-culture with M&phis; downregulated miRNA-155-5p expression, inhibited NF-κB, and reduced the levels of inflammatory factors.Conclusion: PM2.5 promotes M&phis; inflammation by upregulating miRNA-155-5P in exosomes obtained from BEAS-2B cells through miR-155-5P/SOCS1/NF-κB pathway. Exosomal miRNAs mediate cellular communication between BEAS-2B cells and M&phis;, which may be a new mechanism of PM2.5-stimulated pulmonary inflammatory response. Keywords: PM2.5, exosome, microRNA, lung inflammation

Keywords

• pm2.5
• exosome
• microrna
• lung inflammation