Open AccessExosome derived from CD137‐modified endothelial cells regulates the Th17 responses in atherosclerosis
Author(s) -
Xu Liangjie,
Geng Tianxin,
Zang Guangyao,
Bo Li,
Liang Yi,
Zhou Hong,
Yan Jinchuan
Publication year - 2020
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.15130
Subject(s) - inflammation , microbiology and biotechnology , chemistry , exosome , cd137 , monocyte , microvesicles , cancer research , biology , in vitro , immunology , biochemistry , microrna , cytotoxic t cell , gene
The role of exosomes derived from endothelial cells (ECs) in the progression of atherosclerosis (AS) and inflammation remains largely unexplored. We aimed to investigate whether exosome derived from CD137‐modified ECs (CD137‐Exo) played a major role in AS and to elucidate the potential mechanism underlying the inflammatory effect. Exosomes derived from mouse brain microvascular ECs treated with agonist anti‐CD137 antibody were used to explore the effect of CD137 signalling in AS and inflammation in vitro and vivo . CD137‐Exo efficiently induced the progression of AS in ApoE −/− mice. CD137‐Exo increased the proportion of Th17 cells both in vitro and vivo . The IL‐6 contained in CD137‐Exo which is regulated by Akt and NF‐КB pathway was verified to activate Th17 cell differentiation. IL‐17 increased apoptosis, inhibited cell viability and improved lactate dehydrogenase (LDH) release in ECs subjected to inflammation induced by lipopolysaccharide (LPS). The expression of soluble intercellular adhesion molecule1 (sICAM‐1), monocyte chemoattractant protein‐1 (MCP‐1) and E‐selectin in the supernatants of ECs after IL‐17 treatment was dramatically increased. CD137‐Exo promoted the progression of AS and Th17 cell differentiation via NF‐КB pathway mediated IL‐6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS.