Atomic Force Microscopy Study of the Anti-inflammatory Effects of Triptolide on Rheumatoid Arthritis Fibroblast-like Synoviocytes

Microsc Microanal. 2017 Oct;23(5):1002-1012. doi: 10.1017/S1431927617012399. Epub 2017 Jul 26.

Abstract

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.

Keywords: atomic force microscopy; morphology; stiffness; synoviocytes; triptolide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • Arthritis, Rheumatoid / drug therapy*
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Proliferation / drug effects
  • Diterpenes / therapeutic use*
  • Epoxy Compounds / therapeutic use
  • Humans
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Microscopy, Atomic Force / methods*
  • Phenanthrenes / therapeutic use*
  • Synoviocytes / drug effects*
  • Synoviocytes / physiology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • CXCL8 protein, human
  • Diterpenes
  • Epoxy Compounds
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Phenanthrenes
  • Tumor Necrosis Factor-alpha
  • triptolide