Abstract
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.
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Acknowledgements
The authors are thankful for the financial support from the National Nature Science Foundation of China (No. 81370400), Basic research foundation on Shanghai Institute of Science and Technology (10JC1405600), Shanghai Jiaotong University Grants for Interdisciplinary Research on Medicine and Engineering (YG-2014MS74), Research Fund for the Scientific and Technical Project of Shanghai Chest Hospital (2014YZDH20300), and the National Nature Science Foundation of China (No. 81370361).
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11010_2017_3094_MOESM1_ESM.tif
Supplementary material 1 Supplementary Fig. 1 Ghrelin attenuated TNF-α-induced inflammatory factors expression in HUVEC. (A) HUVEC was stimulated with ghrelin (1000 ng/mL or 3000 ng/mL) for 6 hours. MCP-1 mRNA expressions was analyzed by real-time PCR. (B) HUVEC was stimulated with ghrelin (1000 ng/mL or 3000 ng/mL) for 6 hours. IL-1β mRNA expressions was analyzed by real-time PCR. (TIFF 381 kb)
11010_2017_3094_MOESM2_ESM.tif
Supplementary material 2 Supplementary Fig. 2 Ghrelin attenuated TNF-α-induced inflammatory factors expression in THP-1. (A) THP-1 was stimulated with ghrelin (1000 ng/mL or 3000 ng/mL) for 6 hours. IL-8 mRNA expressions was analyzed by real-time PCR. (B) THP-1 was stimulated with ghrelin (1000 ng/mL or 3000 ng/mL) for 6 hours. MCP-1 mRNA expressions was analyzed by real-time PCR. (TIFF 517 kb)
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Zhang, M., Wang, S., Pan, Z. et al. AMPK/NF-κB signaling pathway regulated by ghrelin participates in the regulation of HUVEC and THP1 Inflammation. Mol Cell Biochem 437, 45–53 (2018). https://doi.org/10.1007/s11010-017-3094-x
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DOI: https://doi.org/10.1007/s11010-017-3094-x