Exosomes derived from paeonol-treated monocytes inhibit STAT3-medied inflammatory injury of endothelial cells by up-regulating lipopolysaccharide stimulated exosomal miR-223

[Speaker] Min Dai:1,2,3
[Co-author] Chao Li:1, Xian-Mei Xie:1, Yin Sun:1
1:Anhui University of Chinese Medicine, Hefei, Anhui, China, 2:Nhui Key Laboratory for Research and Development of Traditional Chinese Medicine, Hefei, Anhui, China, 3:Key Laboratory of Xinan Medicine, Ministry of Education, Hefei, Anhui, China

Exosomes involve in regulation of important physiological activities of cells and play an important role in the formation and development of atherosclerosis (AS) by transmiting proteins and miRNAs from cell to cell.Communication between macrophages and endothelial cells is essential for immune and vascular processes.Monocytes/macrophages derived exosomes are dispatched in response to injury,infection and inflammation. Paeonol(Pae),a one of the main active constituent extracted from the Moutan Cortex,possesses multifarious pharmacological actions,particularly an anti-AS effect.Exosomes released by monocytes cells contain a high amount of miR-223 that is shuttled into the endothelial cells in a biologically anti-inflammation effect.However,there is little scientific basis for the role of exosomes derived from monocytes to regulate the function of endothelial cells.Use a traswell system,GW4869 (inhibitors of exosomes release) pretrement with LPS-stimulated THP-1 could attenuate adhesion rate of HUVEC.Pae might alleviate inflammatory damage of HUVEC by regulating THP-1-derived exosomes.To further this finding,we isolated exosomes from THP-1 cells culture medium and co-culture with HUVECs.The treatment of HUVECs with LPS-exosomes caused an increase in STAT3 pathway, negatively promoted endothelial cells of inflammatorydamage.However,Pae-exosomes activated endothelial cells is less damaging.We should that the addition of LPS-exosomes to HUVECs caused an up-regulation of IL-1,IL-6,ICAM-1,VCAM-1 levels.But Pae-exosomes reversed these effect thus attenuating inflammatory damage of HUVEC.After RT-qPCR analysis of exosomes and exosomes treatment HUVECs,We identified and confirmed THP-1-derived exosomal miR-223 inhibits STAT3 pathway in HUVECs.This finding extends our knowledge on how Pae regulates THP-1 exosomal miR-223 reduce inflammatory damage of HUVEC and provides a potential method to prevent AS.
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