Department of Periodontology, Boston University Goldman School of Dental School, Boston, Massachusetts.
J Cell Biochem. 2018 Jul;119(7):6072-6079. doi: 10.1002/jcb.26805. Epub 2018 Apr 10.
TNF-a is an important cytokine mediator of inflammation which suggests that inhibition of TNF activity may provide potential for clinical application. Recent data indicated that treatment of both human and mouse cells with Kavain significantly modulates P. gingivalis- and LPS-induced TNF-α expression. In order to obtain a selective analog with optimized biological activity and structural physico-chemical properties of Kavain, Kavain analogs were designed and synthesized and found one Kavain analogue (named Kav001) that is similar to Kavain but soluble and does not induce a significant toxicity. Both studies in vitro and in vivo treatment by Kav001 showed stronger biological function as compared to Kavain. Furthermore, most mouse bone marrow macrophages up-regulated Bcl-6 while down-regulating LITAF expression after treatment with Kav001 for 36 h. Consequently, this led to an extension of macrophage pseudopods due to its immune response to P.g. infection/LPS stimulation.
肿瘤坏死因子-α（TNF-a）是炎症的重要细胞因子介质，这表明抑制 TNF-a 的活性可能具有临床应用的潜力。最近的数据表明，卡瓦胡椒素（Kavain）处理人类和小鼠细胞可显著调节牙龈卟啉单胞菌（P. gingivalis）和脂多糖（LPS）诱导的 TNF-α表达。为了获得具有优化的生物活性和结构理化性质的选择性类似物，设计并合成了卡瓦胡椒素类似物，并发现了一种卡瓦胡椒素类似物（命名为 Kav001），它与卡瓦胡椒素相似，但可溶且不会引起明显的毒性。Kav001 的体内外研究均显示出比卡瓦胡椒素更强的生物学功能。此外，在 Kav001 处理 36 小时后，大多数小鼠骨髓巨噬细胞上调 Bcl-6 表达，而下调 LITAF 表达。因此，这导致由于其对 P.g. 感染/LPS 刺激的免疫反应，巨噬细胞伪足延长。
