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

作者：Xuefeng Li, Xiaoyan Li, Jing Lin, Xiuyun Sun, Qiuli Ding · 发表于：Journal of Ultrasound in Medicine · 年份：2018 · DOI：10.1002/jum.14898 · 被引用次数：64 · 研究领域：Extracellular vesicles in disease、Ultrasound and Hyperthermia Applications、Vagus Nerve Stimulation Research

OBJECTIVES: Endothelial 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. METHODS: Bone 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)-α-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. RESULTS: The isolated exosomes presented a typical exosomal size of 30 to 100 nm 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 TNFα-induced HUVEC activation and downregulated TNFα-stimulated expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, thus preventing TNFα-induced activation of the nuclear factor-κB signaling pathway. CONCLUSION: Exosomes derived from LIPUS-treated BMDC inhibit TNFα-induced endothelial inflammation by...