Su Zhanhui, Sun Han, Ao Man, Zhao Chunying
Hebei Key Laboratory of Research and Development for Traditional Chinese Medicine, Institute of Chinese Materia Medica, Chengde Medical College, Chengde 067000, China.
Chengde Nursing Vocational College, Chengde 067000, China.
Microsc Microanal. 2017 Oct;23(5):1002-1012. doi: 10.1017/S1431927617012399. Epub 2017 Jul 26.
High-resolution atomic force microscopy (AFM) was used for the in situ evaluation of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of triptolide, based on the morphological and biophysical changes observed in RA-FLS. RA-FLS have been reported to play a primary role in inflammatory bone destruction during the development of RA and thus are regarded as an important target for RA treatment. Triptolide pretreatment significantly inhibited tumor necrosis factor-α-induced expression of the interleukin (IL)-1β, IL-6, and IL-8 genes in MH7A cells. Using AFM, we showed that triptolide-induced morphological damage in MH7A cells by inducing significant ultrastructure changes in the membrane, which were closely related to triptolide-induced apoptosis in MH7A cells. Using force measurements determined with AFM, triptolide was shown to increase the stiffness of MH7A cells. These findings not only revealed the strong anti-inflammatory effects of triptolide on RA-FLS, highlighting triptolide as a potential anti-RA agent, but also revealed the possible use of AFM for studying anti-inflammatory responses in RA-FLS, which we expect to be developed into a potential tool for anti-RA drug studies in RA-FLS.
高分辨率原子力显微镜(AFM)用于原位评估雷公藤甲素对类风湿关节炎(RA)成纤维样滑膜细胞(FLS)的抗炎作用,以基于在RA-FLS中观察到的形态学和生物物理变化来了解雷公藤甲素的抗RA作用。据报道,RA-FLS在RA发展过程中的炎症性骨破坏中起主要作用,因此被视为RA治疗的重要靶点。雷公藤甲素预处理显著抑制了肿瘤坏死因子-α诱导的MH7A细胞中白细胞介素(IL)-1β、IL-6和IL-8基因的表达。使用AFM,我们发现雷公藤甲素通过诱导膜的显著超微结构变化,从而诱导MH7A细胞发生形态损伤,这与雷公藤甲素诱导的MH7A细胞凋亡密切相关。通过AFM进行的力测量显示,雷公藤甲素可增加MH7A细胞的硬度。这些发现不仅揭示了雷公藤甲素对RA-FLS具有强大的抗炎作用,突出了雷公藤甲素作为一种潜在抗RA药物的地位,还揭示了AFM在研究RA-FLS抗炎反应方面的潜在用途,我们期望其能发展成为一种用于RA-FLS抗RA药物研究的潜在工具。