Microglial inflammation is characterized by an increase in proinflammatory cytokines and proinflammatory enzyme levels, facilitating inflammation-mediated neuronal apoptosis. Previous studies indicated that both high-mobility group protein B1 (HMGB1) and E26 transformation-specific sequence (ETS) transcription factor-1 (ESE-1) are involved in lipopolysaccharide (LPS)-mediated neuroinflammation. In the present study, we hypothesized that the ESE-1 modulates HMGB1 expression and is thus involved in LPS-mediated microglial inflammation. Moreover, we explored the potential mechanism by which ESE-1 modulates HMGB1 expression. Our study indicated that LPS increased proinflammatory cytokine and proinflammatory enzyme levels via upregulation of HMGB1 expression in BV2 cells. Moreover, LPS treatment increased ESE-1 expression while inhibiting sirt1 expression. Both sirt1 overexpression and si-ESE-1 treatment reversed LPS-induced HMGB1 expression and proinflammatory cytokine and proinflammatory enzyme levels. In addition, ESE-1 was found to be associated with sirt1. Also ESE-1 and sirt1 were found to be enriched with the HMGB1 promoter region. Sirt1 silencing increased the abundance of ESE-1 that occupied the HMGB1 promoter region. The present study indicated that ESE-1 associates with sirt1 to regulate HMGB1 expression, which participates in LPS-mediated inflammation in BV2 cells.

小胶质细胞炎症的特点是促炎细胞因子和促炎酶水平增加，促进炎症介导的神经元凋亡。先前的研究表明，高迁移率族蛋白 B1 (HMGB1) 和 E26 转化特异性序列 (ETS) 转录因子-1 (ESE-1) 均参与脂多糖 (LPS) 介导的神经炎症。在本研究中，我们假设 ESE-1 调节 HMGB1 表达，从而参与 LPS 介导的小胶质细胞炎症。此外，我们还探讨了ESE-1调节HMGB1表达的潜在机制。我们的研究表明，LPS 通过上调 BV2 细胞中 HMGB1 的表达来增加促炎细胞因子和促炎酶水平。此外，LPS处理增加了ESE-1的表达，同时抑制sirt1的表达。Sirt1过表达和 si-ESE-1 治疗均可逆转 LPS 诱导的 HMGB1 表达以及促炎细胞因子和促炎酶水平。此外，ESE-1被发现与sirt1相关。还发现 ESE-1 和 Sirt1 富含 HMGB1 启动子区域。Sirt1 沉默增加了占据 HMGB1 启动子区域的 ESE-1 的丰度。本研究表明，ESE-1 与 Sirt1 联合调节 HMGB1 表达，参与 BV2 细胞中 LPS 介导的炎症。