Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Rheumatism Research Center, Catholic Institutes of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Int Immunopharmacol. 2017 Nov;52:333-341. doi: 10.1016/j.intimp.2017.09.027. Epub 2017 Oct 6.
Ethyl pyruvate (EP) is the ethyl ester of pyruvate and has antioxidative and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of EP in inflammatory arthritis and to identify the underlying mechanisms.
Mice with collagen-induced arthritis (CIA) were treated with the vehicle control or EP at 20mg/kg, and clinical and histological analyses were performed on the animals. The differentiation of murine CD4+ T cells into T helper 17 (Th17) cells in the presence of EP was investigated in vitro. The effects of EP on osteoclastogenesis were determined by staining for tartrate-resistant acid phosphatase, and measuring the mRNA levels of osteoclastogenesis-related genes. The expression of high-mobility group box 1 (HMGB1) was evaluated after EP therapy using immunohistochemical staining and Western blotting.
EP significantly improved the clinical and histological features of arthritis in CIA mice. EP suppressed the differentiation of CD4+ T cells into Th17 cells, and inhibited the expression of RORγt. The generation of osteoclasts and osteoclastogenic markers from murine and human monocytes was significantly reduced in the presence of EP. The expression of HMGB1 in the synovium was significantly lower in CIA mice treated with EP, compared to control CIA mice. During osteoclastogenesis, HMGB1 release from monocytes was inhibited in the presence of EP.
EP attenuated synovial inflammation and bone destruction in the experimental arthritis model through suppression of IL-17 and HMGB-1. The data suggests that EP could be a novel therapeutic agent for the treatment of inflammatory arthritis, such as rheumatoid arthritis.
丙酮酸乙酯（EP）是丙酮酸的乙酯，具有抗氧化和抗炎作用。本研究旨在评估 EP 在炎症性关节炎中的治疗效果，并确定其潜在机制。
用 vehicle control 或 EP（20mg/kg）处理胶原诱导性关节炎（CIA）小鼠，并对动物进行临床和组织学分析。在存在 EP 的情况下，研究了小鼠 CD4+T 细胞向辅助性 T 细胞 17（Th17）细胞的分化。通过抗酒石酸酸性磷酸酶染色和测量破骨细胞生成相关基因的 mRNA 水平，确定 EP 对破骨细胞生成的影响。用免疫组织化学染色和 Western blot 评估 EP 治疗后高迁移率族蛋白 B1（HMGB1）的表达。
EP 显著改善 CIA 小鼠的关节炎临床和组织学特征。EP 抑制 CD4+T 细胞向 Th17 细胞的分化，并抑制 RORγt 的表达。来自小鼠和人单核细胞的破骨细胞和破骨细胞生成标志物的生成在存在 EP 的情况下显著减少。与对照 CIA 小鼠相比，接受 EP 治疗的 CIA 小鼠滑膜中 HMGB1 的表达明显降低。在破骨细胞生成过程中，EP 抑制单核细胞中 HMGB1 的释放。
EP 通过抑制 IL-17 和 HMGB-1 减轻实验性关节炎模型中的滑膜炎症和骨破坏。数据表明，EP 可能成为治疗炎症性关节炎（如类风湿关节炎）的一种新的治疗剂。
