Thromb Haemost 2014; 112(03): 580-588
DOI: 10.1160/TH13-11-0975
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Role of tumour necrosis factor receptor-1 and nuclear factor-κB in production of TNF-α-induced pro-inflammatory microparticles in endothelial cells

Sung Kyul Lee
1   Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Korea
,
Seung-Hee Yang
1   Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Korea
,
Il Kwon
1   Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Korea
2   Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
3   Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
,
Ok-Hee Lee
1   Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Korea
,
Ji Hoe Heo
1   Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, Yonsei University Health System, Seoul, Korea
2   Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
3   Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
› Author Affiliations

Financial support: This research was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare (HI08C2149) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013R1A1A3011197).
Further Information

Publication History

Received: 25 November 2013

Accepted after major revision: 23 April 2014

Publication Date:
02 December 2017 (online)

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Summary

Tumour necrosis factor-α (TNF-α) is upregulated in many inflammatory diseases and is also a potent agent for microparticle (MP) generation. Here, we describe an essential role of TNF-α in the production of endothelial cell-derived microparticles (EMPs) in vivo and the function of TNF-α-induced EMPs in endothelial cells. We found that TNF-α rapidly increased blood levels of EMPs in mice. Treatment of human umbilical vein endothelial cells (HUVECs) with TNF-α also induced EMP formation in a time-dependent manner. Silencing of TNF receptor (TNFR)-1 or inhibition of the nuclear factor-κB (NF-κB) in HUVECs impaired the production of TNF-α-induced EMP. Incubation of HUVECs with PKH-67-stained EMPs showed that endothelial cells readily engulfed EMPs, and the engulfed TNF-α-induced EMPs promoted the expression of pro-apoptotic molecules and upregulated intercellular adhesion molecule-1 level on the cell surface, which led to monocyte adhesion. Collectively, our findings indicate that the generation of TNF-α-induced EMPs was mediated by TNFR1 or NF-κB and that EMPs can contribute to apoptosis and inflammation of endothelial cells.