Sirt1 ameliorates monosodium urate crystal-induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway
Sirt1 ameliorates monosodium urate crystal-induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway
复制标题
Sirt1 通过 PI3K/Akt/STAT6 通路改变巨噬细胞极化来改善尿酸钠晶体诱导的炎症
DOI：
10.1093/rheumatology/kez165
复制
发表时间：
2019-09-01
期刊：
影响因子：
5.5
通讯作者：
Zou, Hejian
中科院分区：
文献类型：
--
作者：
Liu, Lei;Zhu, Xiaoxia;Zou, Hejian
目标。急性痛风是对MSU晶体的炎症反应。在我们之前的研究中，Sirt1被证明在预防急性痛风炎方面有效果。在目前的研究中，我们旨在研究Sirt1在急性痛风中的潜在机制。观察急性和间歇性痛风患者滑膜细胞学改变和Sirt1的表达。用巨噬细胞、C57BL/6小鼠和Sirt1(+/-)小鼠研究Sirt1对痛风的作用及其机制。SIRT1在急性痛风患者外周血单个核细胞(PBMC)中表达增加，而在慢性痛风组织中未见表达。Sirt1(+/-)小鼠与野生型小鼠相比，痛风模型小鼠损伤足爪组织中的关节炎评分和炎性细胞数量增加。来自小鼠痛风模型的爪子组织的PCR阵列表明，Sirt1的激活可能通过改变巨噬细胞的极化状态来减轻MSU引起的炎症。此外，在急性痛风患者中，关节液涂片中发现巨噬细胞吞噬MSU晶体，滑膜中也发现大量巨噬细胞。痛风小鼠中Sirt1的激活实际上降低了M1极化的趋势。抑制PI3K/AKT可部分阻断Sirt1的抗炎作用和STAT6的转位，并使STAT6的磷酸化表达减少。我们的研究表明，Sirt1通过PI3K/Akt/STAT6通路改变巨噬细胞极化，从而减轻MSU引起的炎症。
Objectives. Acute gout is an inflammatory response to MSU crystals. In our previous research, Sirt1 was shown to have an effect in preventing acute gouty inflammation. In the current study, we aimed to investigate the underlying mechanism involving Sirt1 in acute gout.Methods. The cytological changes and Sirt1 expression in the synovium were observed in patients with acute or intermittent gout. The effect of Sirt1 and its mechanism in gout were studied in macrophages, C57BL/6 mice and Sirt1(+/-) mice.Results. Sirt1 expression was increased in the peripheral blood mononuclear cells (PBMCs) of patients with acute gout but not in the chronic tophus tissue. The arthritis score and numbers of inflammatory cells in injured paw tissue from murine gout models were upregulated in Sirt1(+/-) mice compared with wild-type mice. A PCR array of the paw tissue from murine gout models indicated that Sirt1 activation might attenuate MSU-induced inflammation by altering the polarization state of macrophages. Furthermore, in patients with acute gout, the phagocytosis of MSU crystals by a macrophage was found in a smear of the joint fluid and large amounts of macrophages were also found in the synovium. The activation of Sirt1 in gouty mice actually decreased the tendency toward M1 polarization. The inhibition of PI3K/Akt partially blocked the anti-inflammatory effect of Sirt1 and the translocation of STAT6, and phosphorylated STAT6 expression was decreased in RAW 264.7 cells treated with MSU crystals.Conclusion. Our studies revealed that Sirt1 ameliorates MSU-induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway.