Document Detail

TRAIL induces apoptosis and inflammatory gene expression in human endothelial cells.
MedLine Citation:
PMID:  12874246     Owner:  NLM     Status:  MEDLINE    
Human TRAIL can efficiently kill tumor cells in vitro and kill human tumor xenografts in mice with little effect on normal mouse cells or tissues. The effects of TRAIL on normal human tissues have not been described. In this study, we report that endothelial cells (EC), isolated from human umbilical veins or human dermal microvessels, express death domain-containing TRAIL-R1 and -R2. Incubation with TRAIL for 15 h causes approximately 30% of cultured EC to die, as assessed by propidium iodide uptake. Death is apoptotic, as assessed by Annexin V staining, 4',6'-diamidino-2-phenylindole staining, and DNA fragment ELISA. EC death is increased by cotreatment with cycloheximide but significantly reduced by caspase inhibitors or transduced dominant-negative Fas-associated death domain protein. In surviving cells, TRAIL activates NF-kappaB, induces expression of E-selectin, ICAM-1, and IL-8, and promotes adhesion of leukocytes. Injection of TRAIL into human skin xenografts promotes focal EC injury accompanied by limited neutrophil infiltration. These data suggest that TRAIL is an inducer of tissue injury in humans, an outcome that may influence antitumor therapy with TRAIL.
Jie Hui Li; Nancy C Kirkiles-Smith; Jennifer M McNiff; Jordan S Pober
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  171     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-22     Completed Date:  2003-11-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1526-33     Citation Subset:  AIM; IM    
Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
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MeSH Terms
Apoptosis / genetics,  physiology*
Apoptosis Regulatory Proteins
Cell Line
Endothelium, Vascular / cytology,  metabolism*,  pathology*,  physiology
Gene Expression Regulation / physiology*
HL-60 Cells
Hela Cells
Inflammation Mediators / administration & dosage,  metabolism*,  pharmacology
Injections, Intradermal
Leukocytes, Mononuclear / pathology
Membrane Glycoproteins / administration & dosage,  physiology*
Mice, Inbred C57BL
Mice, SCID
Neutrophil Infiltration / physiology
Receptors, Tumor Necrosis Factor / biosynthesis
Recombinant Proteins / administration & dosage,  pharmacology
Skin Transplantation / pathology
TNF-Related Apoptosis-Inducing Ligand
Transplantation, Heterologous / pathology
Tumor Necrosis Factor-alpha / administration & dosage,  physiology*
Grant Support
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Inflammation Mediators; 0/Membrane Glycoproteins; 0/Receptors, Tumor Necrosis Factor; 0/Recombinant Proteins; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFRSF10A protein, human; 0/TNFSF10 protein, human; 0/Tnfsf10 protein, mouse; 0/Tumor Necrosis Factor-alpha

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