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

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• 作者：Wei Gao ; Haibo Liu ; Jie Yuan ; Chaoneng Wu ; Dong Huang ; Yuanji Ma ; Jianbing Zhu ; Leilei Ma ; Junjie Guo ; Hongtao Shi ; Yunzeng Zou and Junbo Ge
• 刊名：Journal of Cellular and Molecular Medicine
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：20
• 期：12
• 页码：2318-2327
• 全文大小：3209K
• ISSN：1582-4934

文摘

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.