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

Tumour necrosis factor-alpha (TNF-alpha) is upregulated in many inflammatory diseases and is also a potent agent for nnicroparticle (MP) generation. Here, we describe an essential role of TNF-alpha in the production of endothelial cell-derived microparticles (EMPs) in vivo and the function of TNF-alpha-induced EMPs in endothelial cells. We found that TNF-alpha rapidly increased blood levels of EMPs in mice. Treatment of human umbilical vein endothelial cells (HUVECs) with TNF-alpha also induced EMP formation in a time-dependent manner. Silencing of TNF receptor (INFR)-1 or inhibition of the nuclear factor-kappa B (NF-kappa B) in HUVECs impaired the production of TNF-alpha-induced EMP. Incubation of HUVECs with PKH-67-stained EMPs showed that endothelial cells readily engulfed EMPs, and the engulfed TNF-alpha-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-alpha-induced EMPs was mediated by TNFR1 or NF-kappa B and that EMPs can contribute to apoptosis and inflammation of endothelial cells.