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

Thromb Haemost. 2014 Sep 2;112(3):580-8. doi: 10.1160/TH13-11-0975. Epub 2014 Jul 10.


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.

Keywords: Endothelial microparticles; NF-κB; TNF-α; TNFR1; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Adhesion / genetics
  • Cell-Derived Microparticles / immunology*
  • Cell-Derived Microparticles / pathology
  • Cells, Cultured
  • Human Umbilical Vein Endothelial Cells / immunology*
  • Humans
  • Inflammation Mediators / immunology*
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Monocytes / physiology*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • RNA, Small Interfering / genetics
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type I / metabolism*
  • Tumor Necrosis Factor-alpha / immunology
  • Up-Regulation / genetics


  • Apoptosis Regulatory Proteins
  • Inflammation Mediators
  • NF-kappa B
  • RNA, Small Interfering
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1