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, Seung Hee Yang, Il Kwon, Ok Hee Lee, Jihoe Heo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)580-588
Number of pages9
JournalThrombosis and Haemostasis
Volume112
Issue number3
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

NFI Transcription Factors
Tumor Necrosis Factor Receptors
Endothelial Cells
Tumor Necrosis Factor-alpha
Human Umbilical Vein Endothelial Cells
Cell-Derived Microparticles
Receptors, Tumor Necrosis Factor, Type I
Intercellular Adhesion Molecule-1
Monocytes
Apoptosis
Inflammation

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

@article{102d1424213841b4b5e06da572314fd5,
title = "Role of tumour necrosis factor receptor-1 and nuclear factor-κb in production of tnf-α-induced pro-inflammatory microparticles in endothelial cells",
abstract = "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.",
author = "Lee, {Sung Kyul} and Yang, {Seung Hee} and Il Kwon and Lee, {Ok Hee} and Jihoe Heo",
year = "2014",
month = "1",
day = "1",
doi = "10.1160/TH13-11-0975",
language = "English",
volume = "112",
pages = "580--588",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "3",

}

Role of tumour necrosis factor receptor-1 and nuclear factor-κb in production of tnf-α-induced pro-inflammatory microparticles in endothelial cells. / Lee, Sung Kyul; Yang, Seung Hee; Kwon, Il; Lee, Ok Hee; Heo, Jihoe.

In: Thrombosis and Haemostasis, Vol. 112, No. 3, 01.01.2014, p. 580-588.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of tumour necrosis factor receptor-1 and nuclear factor-κb in production of tnf-α-induced pro-inflammatory microparticles in endothelial cells

AU - Lee, Sung Kyul

AU - Yang, Seung Hee

AU - Kwon, Il

AU - Lee, Ok Hee

AU - Heo, Jihoe

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84929963454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929963454&partnerID=8YFLogxK

U2 - 10.1160/TH13-11-0975

DO - 10.1160/TH13-11-0975

M3 - Article

VL - 112

SP - 580

EP - 588

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 3

ER -