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.
authors.forename: S K
authors.initials: SK
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Yang
authors.forename: I
authors.initials: I
authors.lastname: Kwon
authors.affiliation: Ok-Hee Lee, PhD, Severance Integrative Research Institute, for Cerebral and Cardiovascular Diseases, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 120-752, Republic of Korea, Tel.: +82 2 2228 0927, Fax: +82 2 2227 7906, E-mail: okheel@yuhs.ac.
authors.forename: O-H
authors.initials: OH
authors.lastname: Lee
authors.affiliation: Ji Hoe Heo, MD, PhD, Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 120-752, Republic of Korea, Tel.: +82 2 2228 1605, Fax: +82 2 393 0705, E-mail: jhheo@yuhs.ac.
authors.forename: J H
authors.initials: JH
authors.lastname: Heo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; D034741:RNA, Small Interfering; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1
keywords: Endothelial microparticles; NF-κB; TNF-α; TNFR1; inflammation