Open AccessExosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF ‐α mediated NF ‐κB pathway
Author(s) -
Gao Wei,
Liu Haibo,
Yuan Jie,
Wu Chaoneng,
Huang Dong,
Ma Yuanji,
Zhu Jianbing,
Ma Leilei,
Guo Junjie,
Shi Hongtao,
Zou Yunzeng,
Ge Junbo
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12923
Subject(s) - inflammation , microvesicles , microbiology and biotechnology , tumor necrosis factor alpha , nf κb , chemistry , microrna , biology , immunology , biochemistry , gene
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 GW 4869, we demonstrated that mature DC s 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 HUVEC s. 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 DC s derived exosomes increase endothelial inflammation and atherosclerosis via membrane TNF ‐α mediated NF ‐κB pathway. This finding extends our knowledge on how DC s affect inflammation and provides a potential method to prevent endothelial inflammation and atherosclerosis.