The effects of quercetin on erythropoietin, hypoxia-inducible factors-1?, 2?, and pyroptosis related genes expression levels in inflammation induced by TNF-? and LPS in HepG2 cells

Purpose: TNF-alpha, which increases in the circulation as a result of systemic inflammation, suppresses the production of the erythropoiesis regulating hormone, erythropoietin (EPO) and causes inflammation anemia. The anti-inflammatory activity of quercetin has been reported in different studies. However, no study has been found showing the effect of this situation on EPO gene expression. For this purpose, we evaluated the effects of quercetin on inflammation and, more importantly, its effects on EPO, suppressed in the inflammatory environment and Hypoxia-inducible factors (HIF), which are stimulators of EPO synthesis. In addition, we aimed to evaluate the effect of quercetin on pyroptosis, which is defined as pro-inflammatory programmed cell death. Materials and Methods: We created inflammation models with TNF-alpha or LPS using HepG2 cells in vitro. In these inflammation models, we evaluated the effects of quercetin on proinflammatory mediators TNF-alpha, IL-1 alpha, NF-xB gene expressions, EPO, HIF-1 alpha, HIF-2 alpha gene expressions, as well as pyroptosis-related caspase 1 and IL -18 gene expressions. Results: Quercetin showed inflammatory effects by increasing TNF-alpha, IL-1 alpha, and NF-xB mRNA levels. Consistent with this inflammatory effect, EPO mRNA expression was suppressed. HIF-1 alpha and HIF-2 alpha mRNA levels were increased.Conclusion: These results suggested that the increase in HIFs could not prevent the suppressive effect of inflammatory cytokines and NF-xB on EPO production. However, it has been observed that it tends to suppress proinflammatory cell death by decreasing caspase 1 and IL-18 mRNA levels. These results show that quercetin may show conflicting effects, and further studies are needed to test its safety.