The Potential of Fluocinolone Acetonide to Mitigate Inflammation and Lipid Accumulation in 2D and 3D Foam Cell Cultures

Biomed Res Int. 2018 Nov 22;2018:3739251. doi: 10.1155/2018/3739251. eCollection 2018.

Abstract

Inflammation plays an important role in all stages of atherosclerosis development. Therefore, the use of anti-inflammatory drugs could reduce the risk of major adverse cardiovascular events due to atherosclerosis. Herein, we explored the capacity of fluocinolone acetonide (FA), a glucocorticoid (GC), in modulating foam cell formation and response. Human THP-1 derived foam cells were produced using 100 μg/mL oxidized low-density lipoproteins (OxLDL) and fetal bovine serum (1 and 10%). 2D cultures of these cells were treated with FA (0.1, 1, 10, and 50 μg/mL) in comparison with dexamethasone (Dex). Results showed that treatment with 0.1 and 1 μg/mL FA and Dex improved foam cell survival. FA and Dex also inhibited inflammatory cytokine (CD14, M-CSF, MIP-3α, and TNF-α) secretion. Notably, at the concentration of 1 μg/mL, both FA and Dex reduced cholesteryl ester accumulation. Compared to Dex, FA was significantly better in reducing lipid accumulation at the therapeutic concentrations of 1 and 10 μg/mL. In a novel 3D foam cell spheroid model, FA was shown to be more effective than Dex in diminishing lipid accumulation, at the concentration of 0.1 μg/mL. Taken together, FA was demonstrated to be effective in preventing both lipid accumulation and inflammation in foam cells.

MeSH terms

  • Atherosclerosis / drug therapy
  • Atherosclerosis / metabolism
  • Cell Culture Techniques
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Dexamethasone / pharmacology
  • Fluocinolone Acetonide / pharmacology*
  • Foam Cells / drug effects*
  • Foam Cells / metabolism
  • Glucocorticoids / pharmacology
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Lipid Metabolism / drug effects*
  • Lipids / physiology
  • Lipoproteins, LDL / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism

Substances

  • Cytokines
  • Glucocorticoids
  • Lipids
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Fluocinolone Acetonide
  • Dexamethasone