Exosomal miR-2110 from PM2.5-Exposed Lung Epithelial Cells Targets SRSF1 to Promote M1 Macrophage Polarization and Inflammatory Responses in COPD

Yehong Miao,1 Jianjun Gu,1 Juan Li,1 Danye Sheng2 1Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Zhangjiagang First People’s Hospital, Zhangjiagang, People’s Republic of ChinaCorrespondence: Danye Sheng, Email 15895519025@163.comPurpose: Exposure to PM2.5 is a known contributor to the development of chronic obstructive pulmonary disease (COPD). As direct targets of PM2.5, bronchial epithelial cells participate in intercellular communication with macrophages and induce phenotypic changes in these immune cells. This study aimed to investigate the role and underly mechanism of epithelial cell-derived exosomes in regulating macrophage polarization.Methods: Following PM2.5 exposure, exosomes were isolated from BEAS-2B cells and subsequently co-cultured with M0 macrophages. We measured the production of inflammatory cytokines and macrophage markers. The phenotypic effect of miR-2110 on macrophage polarization was examined in a COPD murine model, with subsequent exploration of relevant molecular pathways. The binding specificity of miR-2110 was assessed utilizing a luciferase reporter assay.Results: In vitro analyses confirmed that P-Exo (PM2.5-exposed BEAS-2B cells exosomes) triggered M1 polarization, as evidenced by elevated expression of IL-6, TNF-α, and iNOS-2. Additionally, miR-2110 expression was upregulated in P-Exo. Inhibition of miR-2110 reduced M1 polarization and decreased inflammatory cytokine production both in vitro and in vivo. Luciferase assays confirmed that miR-2110 targeted SRSF1 expression. Overexpression of SRSF1 mitigated the regulatory role of miR-2110 in promoting M1 phenotype transition and pro-inflammatory cytokine production.Conclusion: This work clarifies that exosomal miR-2110, which is produced from lung epithelial cells treated with PM2.5, exacerbates COPD and might be a viable target for COPD prevention and therapy.Keywords: chronic obstructive pulmonary disease, PM2.5, exosomes, macrophage, miR-2110, SRSF1