Division of Rheumatology, Shanghai Medical College, Fudan University, Huashan Hospital, Shanghai, China.
PLoS One. 2011;6(11):e27081. doi: 10.1371/journal.pone.0027081. Epub 2011 Nov 1.
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.
炎症是自身免疫性疾病的主要机制之一，也是大多数疾病的共同特征。适当抑制炎症是治疗疾病的关键。Sirtuin1（Sirt1）已被证明在调节炎症中起作用。白藜芦醇是一种有效的 Sirt1 激活剂，具有抗炎作用。然而，其详细机制尚不完全清楚。在这项研究中，我们研究了 Sirt1 在 NIH/3T3 成纤维细胞系中的抗炎作用。肿瘤坏死因子-α（TNF-α）可诱导 3T3 细胞中基质金属蛋白酶 9（MMP-9）、白细胞介素 1β（IL-1β）、IL-6 和诱导型一氧化氮合酶（iNOS）的过度表达，白藜芦醇以剂量依赖的方式抑制这些促炎分子的过度表达。RNA 干扰敲低 Sirt1 可使 3T3 细胞对 TNF-α刺激敏感，并减弱白藜芦醇的抗炎作用。我们还探讨了白藜芦醇潜在的抗炎机制。白藜芦醇降低了 NF-κB 亚基 RelA/p65 的乙酰化，这明显依赖于 Sirt1。白藜芦醇还减弱了雷帕霉素靶蛋白（mTOR）和 S6 核糖体蛋白（S6RP）的磷酸化，同时减轻了炎症。我们的数据表明，白藜芦醇通过 Sirt1 抑制 TNF-α诱导的炎症。这表明 Sirt1 是调节炎症的有效靶点。这项研究为炎症相关疾病的治疗提供了新的思路。
