Shanghai Chest Hospital, Shanghai Jiaotong University, No. 241 West Huaihai Road, Shanghai, 200030, China.
Dongying People's Hospital, Dongying, 257091, China.
Mol Cell Biochem. 2018 Jan;437(1-2):45-53. doi: 10.1007/s11010-017-3094-x. Epub 2017 Jun 26.
Endothelial inflammation and monocyte plays an essential role in the initiation and progression of atherosclerosis. Ghrelin is beneficial for atherosclerosis progression. However, the detailed and precise molecular mechanisms of how ghrelin regulates endothelial inflammation are not clear. In this study, we investigated the regulation mechanism of ghrelin on TNF-α-activated endothelial inflammation and monocyte adhesion. It was found that TNF-α-induced monocyte adhesion on HUVEC was significantly attenuated by ghrelin. Furthermore, we found that ghrelin effectively suppressed TNF-α-induced inflammatory factors' (including ICAM-1, VCAM-1, MCP-1, and IL-1β) expression through inhibiting AMPK phosphorylation and p65 expression both in HUVEC and THP-1. This phenomenon was further demonstrated by using AMPK agonist AICAR and inhibitor compound C, respectively. Our findings suggest that ghrelin may mediate TNF-α-induced endothelial inflammation and monocyte adhesion, in part via AMPK/NF-κB signaling pathway. These novel anti-inflammatory and immunoregulatory actions of ghrelin may play a certain role in understanding the formation and development of atherosclerosis.
内皮炎症和单核细胞在动脉粥样硬化的发生和发展中起着至关重要的作用。胃饥饿素有利于动脉粥样硬化的进展。然而，胃饥饿素调节内皮炎症的确切分子机制尚不清楚。在这项研究中，我们研究了胃饥饿素对 TNF-α 激活的内皮炎症和单核细胞黏附的调节机制。结果发现，胃饥饿素显著减弱了 TNF-α 诱导的单核细胞在内皮细胞上的黏附。此外，我们发现，胃饥饿素通过抑制 AMPK 磷酸化和 p65 表达，有效抑制了 TNF-α 诱导的炎症因子（包括 ICAM-1、VCAM-1、MCP-1 和 IL-1β）在内皮细胞和 THP-1 中的表达。这一现象分别通过使用 AMPK 激动剂 AICAR 和抑制剂化合物 C 进一步证明。我们的研究结果表明，胃饥饿素可能通过 AMPK/NF-κB 信号通路介导 TNF-α 诱导的内皮炎症和单核细胞黏附。胃饥饿素的这些新的抗炎和免疫调节作用可能在理解动脉粥样硬化的形成和发展中起一定作用。
