Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway

Abstract

Whether dendritic cell (DC) derived exosomes play a role in the progression of endothelial inflammation and atherosclerosis remains unclear. Using a transwell system and exosome release inhibitor GW4869, we demonstrated that mature DCs contributed to endothelial inflammation and exosomes were involved in the process. To further confirm this finding, we isolated exosomes from bone marrow dendritic cell (BMDC) culture medium (named DC‐exos) and stimulated human umbilical vein endothelial cell (HUVEC) with these DC‐exos. We observed that mature DC‐exos increased HUVEC inflammation through NF‐κB pathway in a manner similar to that of lipopolysaccharide. After a protein array analysis of exosomes, we identified and confirmed tumour necrosis factor (TNF)‐α on exosome membrane being the trigger of NF‐κB pathway in HUVECs. We then performed an in vivo study and found that the aorta endothelial of mice could uptake intravenously injected exosomes and was activated by these exosomes. After a period of 12 weeks of mature DC‐exos injection into ApoE−/− mice, the atherosclerotic lesions significantly increased. Our study demonstrates that mature DCs derived exosomes increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway. This finding extends our knowledge on how DCs affect inflammation and provides a potential method to prevent endothelial inflammation and atherosclerosis.

Exosomes Derived From Low‐Intensity Pulsed Ultrasound‐Treated Dendritic Cells Suppress Tumor Necrosis Factor–Induced Endothelial Inflammation

“…Thus, IκBα levels increased by miR‐16 sequestered more NF‐κB proteins in the cytoplasm and alleviated the activity of the signaling pathway. It was reported that the exosomes derived from mature DCs increased endothelial inflammation and atherosclerosis via the membrane TNFα‐mediated NF‐κB signaling pathway . It is feasible that the different results are due to the discrepancy of the packaged contents between exosomes derived from DCs and LIPUS‐treated DCs.…”

Exosomes in Inflammation and Inflammatory Disease

“…In studies conducted by Gao et al., it was found that mature DC‐derived exosomes could increase endothelial inflammation and atherosclerosis in HUVECs via activation of TNF‐α and the NF‐κB pathway. In the ApoE –/– atherosclerotic mouse model, extended treatment with DC‐derived exosomes led to an increase in atherosclerotic plaques . In one study, researchers investigated exosomes derived from vascular smooth muscle cells, which are involved in the formation of atherosclerotic plaques.…”

The multifaceted role of extracellular vesicles in metastasis: Priming the soil for seeding

“…Exosomes have an important role in the physiopathological immune response. In vitro and in vivo assays demonstrated that exosomes released by innate immune cells, stromal cells and adaptive immune cells are critical during inflammation by expanding the pro‐inflammatory response, activating other immune cells . Additionally, they have an important role in the progression of the inflammatory response to resolution, immune tolerance and immunomodulation .…”