The potential of fluocinolone acetonide to mitigate inflammation and lipid accumulation in 2D and 3D foam cell cultures

• Main Authors: Nguyen, Luong T. H., Muktabar, Aristo, Tang, Jinkai, Wong, Yee Shan, Thaxton, Colby S., Venkatraman, Subbu Subramanian, Ng, Kee Woei
• Other Authors: School of Materials Science & Engineering
• Format: Article
• Language: English
• Published: 2019
• Subjects: DRNTU::Engineering::Materials; Lipid Accumulation; Atherosclerosis
• Online Access: https://hdl.handle.net/10356/106089; http://hdl.handle.net/10220/47421
• Institution: Nanyang Technological University

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.