title: 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.
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Wei
authors: W
authors: Gao
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Haibo
authors: H
authors: Liu
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Biomedical Science, Fudan University, Shanghai, China.
authors: Jie
authors: J
authors: Yuan
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Chaoneng
authors: C
authors: Wu
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Dong
authors: D
authors: Huang
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Yuanji
authors: Y
authors: Ma
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Jianbing
authors: J
authors: Zhu
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Leilei
authors: L
authors: Ma
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Junjie
authors: J
authors: Guo
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Hongtao
authors: H
authors: Shi
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Biomedical Science, Fudan University, Shanghai, China.
authors: Yunzeng
authors: Y
authors: Zou
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.|Institute of Biomedical Science, Fudan University, Shanghai, China.
authors: Junbo
authors: J
authors: Ge
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism*; D018920:Coculture Techniques; D003470:Culture Media; D003713:Dendritic Cells / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology*; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D003470:Culture Media; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
keywords: TNF-α; atherosclerosis; dendritic cells; endothelial inflammation; exosomes