INTRODUCTION AND OBJECTIVES Lipopolysaccharide (LPS) is a potent inducer of inflammatory response. Inflammation is a major risk factor for many diseases. Regulation of inflammatory mediator and pro-inflammatory cytokine levels could be a potential therapeutic approach to treat inflammatory injury. The purpose of the present study was to determine whether epalrestat (EPS), which is used for the treatment of diabetic neuropathy, suppresses inflammatory response in LPS-stimulated RAW264.7 cells. MATERIAL AND METHODS The effects of EPS at near-plasma concentration on the levels of pro-inflammatory cytokines and inflammatory mediators was examined using by MTS assay, quantitative RT-PCR analysis, and western blotting in LPS-stimulated RAW264.7 cells. RESULTS EPS suppressed mRNA and protein expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNFα, in RAW264.7 cells stimulated with LPS. EPS also affected inflammatory mediators such as iNOS and NF-κB in LPS-stimulated RAW264.7 cells. CONCLUSIONS In this study, we demonstrated for the first time that EPS suppresses inflammatory response in LPS-stimulated RAW264.7 cells. From these results, we propose that targeting the regulation of pro-inflammatory cytokine levels and inflammatory mediators by EPS is a promising therapeutic approach to treat inflammatory injury. It is expected that EPS, whose safety and pharmacokinetics have been confirmed clinically, would be useful for the treatment of inflammatory diseases.

中文翻译：

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Epalrestat 抑制脂多糖刺激的 RAW264.7 细胞的炎症反应。

引言和目的 脂多糖 (LPS) 是一种有效的炎症反应诱导剂。炎症是许多疾病的主要危险因素。调节炎症介质和促炎细胞因子水平可能是治疗炎症损伤的潜在治疗方法。本研究的目的是确定用于治疗糖尿病神经病变的依帕司他 (EPS) 是否抑制 LPS 刺激的 RAW264.7 细胞的炎症反应。材料和方法 在LPS 刺激的RAW264.7 细胞中，使用MTS 测定、定量RT-PCR 分析和蛋白质印迹检测接近血浆浓度的EPS 对促炎细胞因子和炎症介质水平的影响。结果 EPS 抑制促炎细胞因子的 mRNA 和蛋白表达水平，在 LPS 刺激的 RAW264.7 细胞中包括 IL-1β、IL-6 和 TNFα。EPS 还影响 LPS 刺激的 RAW264.7 细胞中的炎症介质，例如 iNOS 和 NF-κB。结论 在这项研究中，我们首次证明 EPS 可抑制 LPS 刺激的 RAW264.7 细胞的炎症反应。根据这些结果，我们建议通过 EPS 靶向调节促炎细胞因子水平和炎症介质是治疗炎症损伤的有前景的治疗方法。预计EPS的安全性和药代动力学已在临床上得到证实，有望用于治疗炎症性疾病。我们首次证明 EPS 抑制 LPS 刺激的 RAW264.7 细胞中的炎症反应。根据这些结果，我们建议通过 EPS 靶向调节促炎细胞因子水平和炎症介质是治疗炎症损伤的有前景的治疗方法。预计EPS的安全性和药代动力学已在临床上得到证实，有望用于治疗炎症性疾病。我们首次证明 EPS 抑制 LPS 刺激的 RAW264.7 细胞中的炎症反应。根据这些结果，我们建议通过 EPS 靶向调节促炎细胞因子水平和炎症介质是治疗炎症损伤的有前景的治疗方法。预计EPS的安全性和药代动力学已在临床上得到证实，有望用于治疗炎症性疾病。