Liu C.-W.Sung H.-C.Lin S.-R.Wu C.-W.Lee C.-W.Lee I.-T.Yang Y.-F.Yu I.-S.SHU-WHA LINChiang M.-H.Liang C.-J.YUH-LIEN CHEN2020-06-222020-06-2220172045-2322https://scholars.lib.ntu.edu.tw/handle/123456789/503998Resveratrol, an edible polyphenolic phytoalexin, improves endothelial dysfunction and attenuates inflammation. However, the mechanisms have not been thoroughly elucidated. Therefore, we investigated the molecular basis of the effects of resveratrol on TNF-α-induced ICAM-1 expression in HUVECs. The resveratrol treatment significantly attenuated the TNF-α-induced ICAM-1 expression. The inhibition of p38 phosphorylation mediated the reduction in ICAM-1 expression caused by resveratrol. Resveratrol also decreased TNF-α-induced IκB phosphorylation and the phosphorylation, acetylation, and translocation of NF-κB p65. Moreover, resveratrol induced the AMPK phosphorylation and the SIRT1 expression in TNF-α-treated HUVECs. Furthermore, TNF-α significantly suppressed miR-221/-222 expression, which was reversed by resveratrol. miR-221/-222 overexpression decreased p38/NF-κB and ICAM-1 expression, which resulted in reduced monocyte adhesion to TNF-α-treated ECs. In a mouse model of acute TNF-α-induced inflammation, resveratrol effectively attenuated ICAM-1 expression in the aortic ECs of TNF-α-treated wild-type mice. These beneficial effects of resveratrol were lost in miR-221/222 knockout mice. Our data showed that resveratrol counteracted the TNF-α-mediated reduction in miR-221/222 expression and decreased the TNF-α-induced activation of p38 MAPK and NF-κB, thereby suppressing ICAM-1 expression and monocyte adhesion. Collectively, our results show that resveratrol attenuates endothelial inflammation by reducing ICAM-1 expression and that the protective effect was mediated partly through the miR-221/222/AMPK/p38/NF-κB pathway. ? 2017 The Author(s).[SDGs]SDG3antiinflammatory agent; hydroxymethylglutaryl coenzyme A reductase kinase; intercellular adhesion molecule 1; microRNA; MIRN221 microRNA, human; MIRN222 microRNA, human; mitogen activated protein kinase p38; resveratrol; SIRT1 protein, human; sirtuin 1; stilbene derivative; transcription factor RelA; tumor necrosis factor; animal; antagonists and inhibitors; C57BL mouse; cell adhesion; chemically induced; cytology; disease model; drug effect; gene expression regulation; genetics; human; inflammation; knockout mouse; metabolism; monocyte; mouse; pathology; peritonitis; primary cell culture; signal transduction; umbilical vein endothelial cell; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Cell Adhesion; Disease Models, Animal; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Monocytes; p38 Mitogen-Activated Protein Kinases; Peritonitis; Primary Cell Culture; Signal Transduction; Sirtuin 1; Stilbenes; Transcription Factor RelA; Tumor Necrosis Factor-alphajournal article10.1038/srep44689283380092-s2.0-85016160024