High glucose promotes IL-17A-induced gene expression through histone acetylation in retinal pigment epithelium cells

Diabetic retinopathy (DR) is a complication of diabetes mellitus (DM) that can cause visual impairment and blindness. Inflammation plays a critical role in its development and progression. Retinal pigment epithelium (RPE) cells secrete inflammatory factors that modulate ocular immune response. However, it is unclear how diabetes regulates the expression of inflammatory factors in RPE cells. In this study, streptozocin (STZ) was applied to induce diabetic alterations in the retinas of mice, and RPE cells were further purified to profile gene expressions. The IL-17 signaling pathway was the most significantly enriched and the only enriched inflammation pathway in the profile via KEGG analysis. IL-17A induced the expression of targeted genes, which was enhanced by high glucose levels, suggesting a synergistic effect of IL-17A and high glucose. High glucose did not affect the mRNA stability of IL-17A-targeted genes or the activity of IL-17A signaling transduction, but it boosted the histone acetylation on IL-17A-targeted genes. Curcumin, an inhibitor of histone acetyltransferase, abolished high glucose-enhanced histone acetylation of IL-17A-targeted genes and blocked the promotion of high glucose levels on gene expression induced by IL-17A. In conclusion, high glucose levels promote IL-17A-induced gene expression via histone acetylation in RPE cells.