Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts

Inflammation is one of main mechanisms of autoimmune disorders and a common feature of most diseases. Appropriate suppression of inflammation is a key resolution to treat the diseases. Sirtuin1 (Sirt1) has been shown to play a role in regulation of inflammation. Resveratrol, a potent Sirt1 activator...

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Main Authors:	Zhu, Xiaoxia, Liu, Qiong, Wang, Meimei, Liang, Minrui, Yang, Xue, Xu, Xue, Zou, Hejian, Qiu, Jianhua
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206084/

id	pubmed-3206084
recordtype	oai_dc
spelling	pubmed-32060842011-11-08 Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts Zhu, Xiaoxia Liu, Qiong Wang, Meimei Liang, Minrui Yang, Xue Xu, Xue Zou, Hejian Qiu, Jianhua Research Article Inflammation is one of main mechanisms of autoimmune disorders and a common feature of most diseases. Appropriate suppression of inflammation is a key resolution to treat the diseases. Sirtuin1 (Sirt1) has been shown to play a role in regulation of inflammation. Resveratrol, a potent Sirt1 activator, has anti-inflammation property. However, the detailed mechanism is not fully understood. In this study, we investigated the anti-inflammation role of Sirt1 in NIH/3T3 fibroblast cell line. Upregulation of matrix metalloproteinases 9 (MMP-9), interleukin-1beta (IL-1β), IL-6 and inducible nitric oxide synthase (iNOS) were induced by tumor necrosis factor alpha (TNF-α) in 3T3 cells and resveratrol suppressed overexpression of these pro-inflammatory molecules in a dose-dependent manner. Knockdown of Sirt1 by RNA interference caused 3T3 cells susceptible to TNF-α stimulation and diminished anti-inflammatory effect of resveratrol. We also explored potential anti-inflammatory mechanisms of resveratrol. Resveratrol reduced NF-κB subunit RelA/p65 acetylation, which is notably Sirt1 dependent. Resveratrol also attenuated phosphorylation of mammalian target of rapamycin (mTOR) and S6 ribosomal protein (S6RP) while ameliorating inflammation. Our data demonstrate that resveratrol inhibits TNF-α-induced inflammation via Sirt1. It suggests that Sirt1 is an efficient target for regulation of inflammation. This study provides insight on treatment of inflammation-related diseases. Public Library of Science 2011-11-01 /pmc/articles/PMC3206084/ /pubmed/22069489 http://dx.doi.org/10.1371/journal.pone.0027081 Text en Zhu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhu, Xiaoxia Liu, Qiong Wang, Meimei Liang, Minrui Yang, Xue Xu, Xue Zou, Hejian Qiu, Jianhua
spellingShingle	Zhu, Xiaoxia Liu, Qiong Wang, Meimei Liang, Minrui Yang, Xue Xu, Xue Zou, Hejian Qiu, Jianhua Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts
author_facet	Zhu, Xiaoxia Liu, Qiong Wang, Meimei Liang, Minrui Yang, Xue Xu, Xue Zou, Hejian Qiu, Jianhua
author_sort	Zhu, Xiaoxia
title	Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts
title_short	Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts
title_full	Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts
title_fullStr	Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts
title_full_unstemmed	Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts
title_sort	activation of sirt1 by resveratrol inhibits tnf-α induced inflammation in fibroblasts
description	Inflammation is one of main mechanisms of autoimmune disorders and a common feature of most diseases. Appropriate suppression of inflammation is a key resolution to treat the diseases. Sirtuin1 (Sirt1) has been shown to play a role in regulation of inflammation. Resveratrol, a potent Sirt1 activator, has anti-inflammation property. However, the detailed mechanism is not fully understood. In this study, we investigated the anti-inflammation role of Sirt1 in NIH/3T3 fibroblast cell line. Upregulation of matrix metalloproteinases 9 (MMP-9), interleukin-1beta (IL-1β), IL-6 and inducible nitric oxide synthase (iNOS) were induced by tumor necrosis factor alpha (TNF-α) in 3T3 cells and resveratrol suppressed overexpression of these pro-inflammatory molecules in a dose-dependent manner. Knockdown of Sirt1 by RNA interference caused 3T3 cells susceptible to TNF-α stimulation and diminished anti-inflammatory effect of resveratrol. We also explored potential anti-inflammatory mechanisms of resveratrol. Resveratrol reduced NF-κB subunit RelA/p65 acetylation, which is notably Sirt1 dependent. Resveratrol also attenuated phosphorylation of mammalian target of rapamycin (mTOR) and S6 ribosomal protein (S6RP) while ameliorating inflammation. Our data demonstrate that resveratrol inhibits TNF-α-induced inflammation via Sirt1. It suggests that Sirt1 is an efficient target for regulation of inflammation. This study provides insight on treatment of inflammation-related diseases.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206084/
_version_	1611484976097787904

Activation of Sirt1 by Resveratrol Inhibits TNF-α Induced Inflammation in Fibroblasts

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