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

ObjectivesEndothelial cell inflammation plays an important role in atherosclerosis. Low-intensity pulsed ultrasonography (LIPUS) exerts an anti-inflammatory function on endothelial cells, whereas the underlying mechanism has not been fully elucidated. MethodsBone marrow dendritic cells (BMDCs) derived from bone barrow cells were treated with LIPUS, and exosomes secreted into the supernatant were purified. The isolated exosomes were incubated with human umbilical vein endothelial cells (HUVECs) to investigate their effect on tumor necrosis factor (TNF)-alpha-induced endothelial inflammation. Ultrastructure was analyzed by transmission electron microscopy. Messenger RNA levels were determined by quantitative reverse transcription polymerase chain reaction, and protein levels were analyzed by western blot. ResultsThe isolated exosomes presented a typical exosomal size of 30 to 100nm in diameter and expressed exosome positive markers (Alix, CD63, and TSG101) but not the exosome negative marker (Calnexin). Exosomes derived from LIPUS-treated BMDCs were rich in miR-16 and miR-21, which could be engulfed by HUVECs. Pretreatment with exosomes impeded TNF alpha-induced HUVEC activation and downregulated TNF alpha-stimulated expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, thus preventing TNF alpha-induced activation of the nuclear factor-kappa B signaling pathway. ConclusionExosomes derived from LIPUS-treated BMDC inhibit TNF alpha-induced endothelial inflammation by inhibiting the nuclear factor-kappa B signaling pathway.