Lipopolysaccharide and interferon-gamma enhance Fas-mediated cell death in mouse vascular endothelial cells via augmentation of Fas expression.
The effect of interferon (IFN)-gamma and/or lipopolysaccharide (LPS) on Fas-mediated cell death with anti-Fas agonistic antibody in vascular endothelial cells was examined using a mouse END-D cell line. Anti-Fas agonistic antibody exhibited cytotoxic actions on END-D cells. Fas-mediated cell death was enhanced by LPS or IFN-gamma. The combination of IFN-gamma and LPS significantly enhanced cell death compared to IFN-gamma or LPS alone. IFN-gamma and LPS augmented cell surface expression of Fas, but not tumour necrosis factor (TNF) receptor 1. Inhibitors of p38 mitogen-activated protein kinase (MAPK) prevented augmentation of Fas expression in IFN-gamma and LPS-treated END-D cells. IFN-gamma and LPS-treated END-D cells did not become susceptible to TNF-alpha or nitric oxide-mediated cytotoxicity. IFN-gamma and LPS thus appear to augment selectively Fas expression via activation of p38 MAPK and enhance Fas-mediated cell death in END-D cells. Furthermore, administration of IFN-gamma and LPS into mice induced in vivo expression of Fas on vascular endothelial cells and Fas ligand (FasL) on peripheral blood leucocytes. The relationship between enhancement of Fas-mediated cell death by IFN-gamma and LPS and the development of vascular endothelial injury is discussed.
Koide
N
N
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. koide@aichi-med-u.ac.jp
Morikawa
A
A
Tumurkhuu
G
G
Dagvadorj
J
J
Hassan
F
F
Islam
S
S
Naiki
Y
Y
Mori
I
I
Yoshida
T
T
Yokochi
T
T
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D053222:Fas Ligand Protein / Q000097:blood / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000276:immunology; D019014:fas Receptor / Q000276:immunology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D019014:fas Receptor; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases