@article{5848a06f492d4d00ab07f2398b29c034,
title = "Resveratrol attenuates ICAM-1 expression and monocyte adhesiveness to TNF-α-treated endothelial cells: Evidence for an anti-inflammatory cascade mediated by the MIR-221/222/AMPK/p38/NF-7kappa;B pathway",
abstract = "Resveratrol, 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.",
author = "Liu, {Chen Wei} and Sung, {Hsin Ching} and Lin, {Shu Rung} and Wu, {Chun Wei} and Lee, {Chiang Wen} and I-Ta Lee and Yang, {Yi Fan} and Yu, {I. Shing} and Lin, {Shu Wha} and Chiang, {Ming Hsien} and Liang, {Chan Jung} and Chen, {Yuh Lien}",
note = "Funding Information: This work was supported in part by grants from the Ministry of Science and Technology (NSC 102-2628-B-002-001-MY3 to YLC; NSC 102-2320-B-033-003 to SRL), Excellent Research Projects of National Taiwan University (Grant Nos 97R0066-08, 98R0066-08, and 99R81810 to SWL), and Kaohsiung Medical University (Aim for the Top University Grant, Grant No. KMU-TP104D00), Taiwan. We acknowledge the technical services provided by the {"}Transgenic Mouse Model Core Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology, Taiwan{"} and the {"}Gene Knockout Mouse Core Laboratory of National Taiwan University Center of Genomic Medicine{"}. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = mar,
day = "24",
doi = "10.1038/srep44689",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}