Duality of Valproic Acid Effects on Inflammation, Oxidative Stress and Autophagy in Human Eosinophilic Cells

Eosinophils function in rapid innate immune responses and allergic reactions. Recent research has raised the possibility that the histone deacetylase inhibitor valproic acid (VPA) may be a promising therapeutic agent for treatment of allergic responses and certain cancers. However, its effects on eosinophils remain unclear. Utilizing the EoL-1 human eosinophil cell line as a model, we investigated the effects of VPA on oxidative stress- and autophagy-mediated immune responses. We found that VPA induced reactive oxidative species (ROS) generation and eosinophil activation without affecting cell viability. Moreover, VPA treatment suppressed the negative regulator of antioxidant transcription factor Nrf2, which is known to activate antioxidant defense. Interestingly, VPA was able to increase autophagic markers, as well as NLRP3 and NLRC4 mRNA activation, in Eol-1 cells in a dose-dependent manner. Collectively, our results indicate that VPA could increase the severity of allergic responses, and if so, it clearly would not be a suitable drug for the treatment of allergic reactions. However, VPA does have the potential to induce autophagy and to regulate the inflammatory responses via inflammasome-driven caspase-1 deactivation in a dose-dependent manner.