PMID- 32149463 OWN - NLM STAT- MEDLINE DCOM- 20210429 LR - 20210429 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 24 IP - 8 DP - 2020 Apr TI - Exosome derived from CD137-modified endothelial cells regulates the Th17 responses in atherosclerosis. PG - 4659-4667 LID - 10.1111/jcmm.15130 [doi] AB - 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-capital KA, CyrillicB 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-capital KA, CyrillicB pathway mediated IL-6 expression. This finding provided a potential method to prevent local and peripheral inflammation in AS. CI - (c) 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Xu, Liangjie AU - Xu L AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Geng, Tianxin AU - Geng T AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Zang, Guangyao AU - Zang G AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Bo, Li AU - Bo L AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Liang, Yi AU - Liang Y AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Zhou, Hong AU - Zhou H AD - School of Medicine, Jiangsu University, Zhenjiang, China. FAU - Yan, Jinchuan AU - Yan J AUID- ORCID: 0000-0001-6050-8007 AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200309 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Apolipoproteins E) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Tnfrsf9 protein, mouse) RN - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 9) SB - IM MH - Animals MH - Apolipoproteins E/*genetics MH - Atherosclerosis/chemically induced/*genetics/pathology MH - Brain/metabolism/pathology MH - Cell Differentiation/genetics MH - Endothelial Cells/metabolism/pathology MH - Exosomes/*genetics MH - Gene Expression Regulation/genetics MH - Humans MH - Inflammation/chemically induced/*genetics/pathology MH - Lipopolysaccharides/toxicity MH - Mice MH - Mice, Knockout MH - NF-kappa B/genetics MH - Signal Transduction/genetics MH - Th17 Cells/metabolism/pathology MH - Tumor Necrosis Factor Receptor Superfamily, Member 9/*genetics PMC - PMC7176883 OTO - NOTNLM OT - atherosclerosis OT - endothelial cells; Th17 cells OT - exosomes COIS- The authors declare that they have no conflict of interest. EDAT- 2020/03/10 06:00 MHDA- 2021/04/30 06:00 PMCR- 2020/04/01 CRDT- 2020/03/10 06:00 PHST- 2019/10/27 00:00 [received] PHST- 2020/01/13 00:00 [revised] PHST- 2020/01/23 00:00 [accepted] PHST- 2020/03/10 06:00 [pubmed] PHST- 2021/04/30 06:00 [medline] PHST- 2020/03/10 06:00 [entrez] PHST- 2020/04/01 00:00 [pmc-release] AID - JCMM15130 [pii] AID - 10.1111/jcmm.15130 [doi] PST - ppublish SO - J Cell Mol Med. 2020 Apr;24(8):4659-4667. doi: 10.1111/jcmm.15130. Epub 2020 Mar 9.