Laboratory of Health Science, Postgraduate Program in Health Science, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil; Instituto Federal de Minas Gerais (IFMG), Ouro Preto, Minas Gerais, Brazil.
Bachelor Degree in Biology, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil.
Cytokine Growth Factor Rev. 2017 Dec;38:98-105. doi: 10.1016/j.cytogfr.2017.11.001. Epub 2017 Nov 7.
The regulation of chronic inflammation has received considerable research attention in recent years because of its contribution to the pathogenesis of chronic diseases such as arthritis, diabetes, metabolic syndrome and obesity. Thus, strategies that inhibit the inflammatory state may be beneficial in improving the pathophysiology of several inflammation-related disorders. Sirtuins are a family of histone deacetylases that contain seven enzymatic activities in mammals (SIRT1-SIRT7) and function to suppress gene transcription by epigenetic mechanisms. Nuclear sirtuins (SIRT 1, 2, 6 and 7) in particular may play an important role in the regulation of inflammatory responses. In the present review, we assessed the roles of nuclear sirtuins in inflammatory reactions: SIRT1 has been shown to suppress NF-κb activity, the master regulator of cellular inflammatory response, decrease COX-2 and iNOS production, and increase antioxidant gene expression that suppressed inflammation. SIRT2 activity included the deacetylation of p65 subunit of NF-κβ and RIP-1, while SIRT6 has been shown to interact with p65/RelA bound to the NF-κβ promoter region and repress transcriptional activity. Furthermore, recent studies have shown that the absence of SIRT7 produced an increase in inflammation, illustrating that SIRT7 also functioned to decrease inflammation. Given their significant roles in the regulation of chronic inflammation, nuclear sirtuins represent potential therapeutic targets in the control of chronic inflammatory diseases.
近年来，慢性炎症的调节受到了相当多的研究关注，因为它有助于关节炎、糖尿病、代谢综合征和肥胖等慢性疾病的发病机制。因此，抑制炎症状态的策略可能有益于改善几种与炎症相关的疾病的病理生理学。Sirtuins 是一组组蛋白去乙酰化酶，在哺乳动物中包含七种酶活性（SIRT1-SIRT7），通过表观遗传机制抑制基因转录。核 Sirtuins（SIRT1、2、6 和 7）特别可能在调节炎症反应中发挥重要作用。在本综述中，我们评估了核 Sirtuins 在炎症反应中的作用：SIRT1 已被证明可抑制 NF-κb 活性，这是细胞炎症反应的主要调节剂，减少 COX-2 和 iNOS 的产生，并增加抑制炎症的抗氧化基因表达。SIRT2 活性包括 NF-κβ 和 RIP-1 的 p65 亚基的去乙酰化，而 SIRT6 已被证明与 NF-κβ 启动子区域结合的 p65/RelA 相互作用并抑制转录活性。此外，最近的研究表明，SIRT7 的缺失会导致炎症增加，表明 SIRT7 也具有降低炎症的作用。鉴于它们在慢性炎症调节中的重要作用，核 Sirtuins 代表了控制慢性炎症性疾病的潜在治疗靶点。
