title: Resveratrol Protects against TNF-α-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and p38 MAPK.
abstract: Inflammation and reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerosis. Resveratrol has been shown to possess anti-inflammatory and antioxidative stress activities, but the underlying mechanisms are not fully understood. In the present study, we investigated the molecular basis associated with the protective effects of resveratrol on tumor necrosis factor-alpha (TNF-α)-induced injury in human umbilical endothelial cells (HUVECs) using a variety of approaches including a cell viability assay, reverse transcription and quantitative polymerase chain reaction, western blot, and immunofluorescence staining. We showed that TNF-α induced CD40 expression and ROS production in cultured HUVECs, which were attenuated by resveratrol treatment. Also, resveratrol increased the expression of sirtuin 1 (SIRT1); and repression of SIRT1 by small-interfering RNA (siRNA) and the SIRT1 inhibitor Ex527 reduced the inhibitory effects of resveratrol on CD40 expression and ROS generation. In addition, resveratrol downregulated the levels of p65 and phospho-p38 MAPK, but this inhibitory effect was attenuated by the suppression of SIRT1 activity. Moreover, the p38 MAPK inhibitor SD203580 and the nuclear factor (NF)-κB inhibitor pyrrolidine dithiocarbamate (PDTC) achieved similar repressive effects as resveratrol on TNF-α-induced ROS generation and CD40 expression. Thus, our study provides a mechanistic link between resveratrol and the activation of SIRT1, the latter of which is involved in resveratrol-mediated repression of the p38 MAPK/NF-κB pathway and ROS production in TNF-α-treated HUVECs.
authors.affiliation: Provincial Clinical Medical College, Fujian Medical University, Fuzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.affiliation: Provincial Clinical Medical College, Fujian Medical University, Fuzhou, China.|Department of Geriatrics, Fujian Provincial Hospital Key Laboratory of Geriatrics, Fujian Medical University, Fuzhou, China.|Fujian Institute of Clinical Geriatrics, Fuzhou, China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Yu
authors.affiliation: Fujian Institute of Clinical Geriatrics, Fuzhou, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Huang
authors.affiliation: Provincial Clinical Medical College, Fujian Medical University, Fuzhou, China.|Fujian Institute of Clinical Geriatrics, Fuzhou, China.
authors.forename: Pengli
authors.initials: P
authors.lastname: Zhu
mesh_terms: D019013:CD40 Antigens / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D019013:CD40 Antigens; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol