Effects of Suberoylanilide Hydroxamic Acid (SAHA) on the Inflammatory Response in Lipopolysaccharide-Induced N9 Microglial Cells

Introduction: Epigenetics has shown promising results for understanding the different behaviors of microglia under the context of neuroinflammation. However, to our knowledge, the results of this complex mechanism with novel pharmacological agents such as histone deacetylase inhibitors (HDACis) are still missing. In this study, we aimed to investigate the effects of suberoylanilide hydroxamic acid (SAHA), a pan-HDACi, on the lipopolysaccharide (LPS)-induced neuroinflammation model in the N9 microglial cells. Methods: Microglial cells were treated with SAHA (0.25, 0.5, 1.0, 1.25, 1.5 µM) and LPS (100 ng/mL) for 24 hours. Then, levels of the pro/anti-inflammatory cytokines interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), and IL-10 were determined by the enzyme-linked immunosorbent assay. The total cellular HDAC activity was determined by colorimetric analysis. Additionally, the expression levels of nuclear factor kappa-B (NF-κB) were quantified via western blotting. Results: SAHA (1.0 and 1.25 µM) attenuated the LPS-induced inflammatory response of microglial cells via decreasing NF-κB expression and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in the N9 microglial cells. Moreover, SAHA treatment improved IL-10 levels and prevented the LPS-induced increase in the HDAC activity in the microglial cells. Conclusion: Our results suggest SAHA attenuates the LPS-induced inflammatory response in the N9 microglial cells, and regulation of histone acetylation with HDACis might be a rational approach for the treatment of neuroinflammation.