Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, Texas 76502, USA.
Mol Ther. 2012 Jan;20(1):14-20. doi: 10.1038/mt.2011.211. Epub 2011 Oct 18.
Recent observations have demonstrated that one of the functions of mesenchymal stem/stromal cells (MSCs) is to serve as guardians against excessive inflammatory responses. One mode of action of the cells is that they are activated to express the interleukin (IL)-1 receptor antagonist. A second mode of action is to create a negative feedback loop in which tumor necrosis factor-α (TNF-α) and other proinflammatory cytokines from resident macrophages activate MSCs to secrete the multifunctional anti-inflammatory protein TNF-α stimulated gene/protein 6 (TSG-6). The TSG-6 then reduces nuclear factor-κB (NF-κB) signaling in the resident macrophages and thereby modulates the cascade of proinflammatory cytokines. A third mode of action is to create a second negative feedback loop whereby lipopolysaccharide, TNF-α, nitric oxide, and perhaps other damage-associated molecular patterns (DAMPs) from injured tissues and macrophages activate MSCs to secrete prostaglandin E(2) (PGE(2)). The PGE(2) converts macrophages to the phenotype that secretes IL-10. There are also suggestions that MSCs may produce anti-inflammatory effects through additional modes of action including activation to express the antireactive oxygen species protein stanniocalcin-1.
最近的观察表明，间充质干细胞（MSCs）的功能之一是充当对抗过度炎症反应的守护者。细胞的一种作用方式是被激活表达白细胞介素（IL）-1 受体拮抗剂。第二种作用方式是创建负反馈回路，其中驻留巨噬细胞中的肿瘤坏死因子-α（TNF-α）和其他促炎细胞因子激活 MSCs 分泌多功能抗炎蛋白 TNF-α刺激基因/蛋白 6（TSG-6）。然后，TSG-6 降低驻留巨噬细胞中的核因子-κB（NF-κB）信号传导，从而调节促炎细胞因子的级联反应。第三种作用方式是创建第二个负反馈回路，其中来自受伤组织和巨噬细胞的脂多糖、TNF-α、一氧化氮，也许还有其他损伤相关分子模式（DAMPs）激活 MSCs 分泌前列腺素 E（PGE（2））。PGE（2）将巨噬细胞转化为分泌 IL-10 的表型。也有研究表明，MSCs 可能通过其他作用方式产生抗炎作用，包括激活表达抗活性氧物质蛋白 stanniocalcin-1。
