State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Mol Ther. 2011 Oct;19(10):1849-57. doi: 10.1038/mt.2011.82. Epub 2011 May 10.
Nuclear factor-κB (NF-κB) is a central regulator of immune response and a potential target for developing anti-inflammatory agents. Mechanistic studies suggest that compounds that directly inhibit NF-κB DNA binding may block inflammation and the associated tissue damage. Thus, we attempted to discover peptides that could interfere with NF-κB signaling based on a highly conserved DNA-binding domain found in all NF-κB members. One such small peptide, designated as anti-inflammatory peptide-6 (AIP6), was characterized in the current study. AIP6 directly interacted with p65 and displayed an intrinsic cell-penetrating property. This peptide demonstrated significant anti-inflammatory effects in vitro and in vivo. In vitro, AIP6 inhibited the DNA-binding and transcriptional activities of the p65 NF-κB subunit as well as the production of inflammatory mediators in macrophages upon stimulation. Local administration of AIP6 significantly inhibited inflammation induced by zymosan in mice. Collectively, our results suggest that AIP6 is a promising lead peptide for the development of specific NF-κB inhibitors as potential anti-inflammatory agents.
核因子-κB（NF-κB）是免疫反应的核心调节剂，也是开发抗炎药物的潜在靶点。机制研究表明，直接抑制 NF-κB DNA 结合的化合物可能阻断炎症及其相关的组织损伤。因此，我们试图基于所有 NF-κB 成员中发现的高度保守的 DNA 结合结构域，发现可以干扰 NF-κB 信号的肽。当前研究中鉴定了一种这样的小肽，称为抗炎肽 6（AIP6）。AIP6 直接与 p65 相互作用，并具有内在的细胞穿透特性。该肽在体外和体内均显示出显著的抗炎作用。体外，AIP6 抑制刺激后巨噬细胞中 p65 NF-κB 亚基的 DNA 结合和转录活性以及炎症介质的产生。局部给予 AIP6 可显著抑制酵母聚糖诱导的小鼠炎症。总之，我们的结果表明，AIP6 是一种有前途的先导肽，可用于开发特异性 NF-κB 抑制剂作为潜在的抗炎药物。
