当前位置: X-MOL 学术Int. Immunopharmacol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The dipeptidyl peptidase (DPP)-4 inhibitor trelagliptin inhibits IL-1β-induced endothelial inflammation and monocytes attachment
International Immunopharmacology ( IF 4.8 ) Pub Date : 2020-10-10 , DOI: 10.1016/j.intimp.2020.106996
Jinxiu Meng , Weilan Zhang , Chanjuan Wang , Sanjun Xiong , Qiushi Wang , Hanpin Li , Gang Liu , Zhimin Hao

Cardiovascular diseases remain the major cause of death worldwide. Atherosclerosis is recognized as the common ground of cardiovascular diseases. Inflammatory cytokines-induced attachment of monocytes to endothelial cells is a significant event in the progression of atherosclerosis. As a highly selective dipeptidyl peptidase (DPP)-4 inhibitor, trelagliptin is used for the treatment of type 2 diabetes mellitus (T2DM). However, whether trelagliptin possesses an inhibitory effect on endothelial dysfunction and monocyte adhesion is unknown. In the current study, we tested the effect of trelagliptin in endothelial cells. We used human aortic endothelial cells (HAECs) exposed to interleukin (IL)-1β to mimic the microenvironment of atherosclerosis. Our results showed that trelagliptin inhibited the expression of pro-inflammatory chemokines including monocyte chemoattractant protein 1 (MCP-1), CXCL-1, and IL-6. Furthermore, trelagliptin suppressed the expression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Mechanistically, trelagliptin suppressed the activation of activator protein-1 (AP-1) and NF-κB signaling pathways, which modulate the inflammatory process and monocyte adhesion. Collectively, our results showed that trelagliptin had a powerful inhibitory effect on the attachment of monocytes to endothelial cells, indicating that trelagliptin might have a protective effect on cardiovascular diseases such as atherosclerosis.



中文翻译:

二肽基肽酶(DPP)-4抑制剂曲格列汀抑制IL-1β诱导的内皮炎症和单核细胞附着

心血管疾病仍然是世界范围内主要的死亡原因。动脉粥样硬化被认为​​是心血管疾病的共同基础。炎性细胞因子诱导的单核细胞附着于内皮细胞是动脉粥样硬化进展中的重要事件。作为一种高度选择性的二肽基肽酶(DPP)-4抑制剂,曲拉格列汀用于治疗2型糖尿病(T2DM)。然而,曲拉格列汀是否对内皮功能障碍和单核细胞粘附具有抑制作用尚不清楚。在当前的研究中,我们测试了曲拉格列汀在内皮细胞中的作用。我们使用暴露于白介素(IL)-1β的人主动脉内皮细胞(HAEC)来模拟动脉粥样硬化的微环境。我们的结果表明,曲拉格列汀抑制促炎性趋化因子的表达,包括单核细胞趋化蛋白1(MCP-1),CXCL-1和IL-6。此外,曲拉格列汀抑制粘附分子的表达,例如血管细胞粘附分子-1(VCAM-1)和细胞间粘附分子-1(ICAM-1)。从机械上讲,海藻糖素抑制激活蛋白1(AP-1)和NF-κB信号通路的激活,从而调节炎症过程和单核细胞粘附。总体而言,我们的结果表明,曲拉格列汀对单核细胞与内皮细胞的附着具有强大的抑制作用,表明曲拉格列汀可能对心血管疾病(如动脉粥样硬化)具有保护作用。海藻糖素抑制血管细胞粘附分子-1(VCAM-1)和细胞间粘附分子-1(ICAM-1)等粘附分子的表达。从机械上讲,海藻糖素抑制激活蛋白1(AP-1)和NF-κB信号通路的激活,从而调节炎症过程和单核细胞粘附。总体而言,我们的结果表明,曲拉格列汀对单核细胞与内皮细胞的附着具有强大的抑制作用,表明曲拉格列汀可能对心血管疾病(如动脉粥样硬化)具有保护作用。海藻糖素抑制血管细胞粘附分子-1(VCAM-1)和细胞间粘附分子-1(ICAM-1)等粘附分子的表达。从机械上讲,海藻糖素抑制激活蛋白1(AP-1)和NF-κB信号通路的激活,从而调节炎症过程和单核细胞粘附。总体而言,我们的结果表明,曲拉格列汀对单核细胞与内皮细胞的附着具有强大的抑制作用,表明曲拉格列汀可能对心血管疾病(如动脉粥样硬化)具有保护作用。调节炎症过程和单核细胞粘附。总体而言,我们的结果表明,曲拉格列汀对单核细胞与内皮细胞的附着具有强大的抑制作用,表明曲拉格列汀可能对心血管疾病(如动脉粥样硬化)具有保护作用。调节炎症过程和单核细胞粘附。总体而言,我们的结果表明,曲拉格列汀对单核细胞与内皮细胞的附着具有强大的抑制作用,表明曲拉格列汀可能对心血管疾病(如动脉粥样硬化)具有保护作用。

更新日期:2020-10-11
down
wechat
bug