Oxidized LDL enhances lipopolysaccharide-induced tissue factor expression in human adherent monocytes.
Oxidized low-density lipoprotein (oxLDL) has been characterized as an atherogenic molecule responsible for the induction of a variety of gene products. One such gene, tissue factor (TF), the cellular initiator of the coagulation cascade, is not expressed in normal vascular tissue but is expressed by monocytes and foam cells in atherosclerotic lesions. Therefore, we examined the effect of oxLDL on TF expression in cultured human adherent monocytes. Endotoxin-free oxLDL alone did not induce TF expression in adherent monocytes. However, oxLDL significantly enhanced TF expression induced by the inflammatory mediator, bacterial lipopolysaccharide (LPS), in a time- and dose-dependent manner. In contrast, oxLDL did not alter LPS-mediated production of interleukin-8 and actually inhibited LPS-induced secretion of tumor necrosis factor-alpha, suggesting that some aspects of the signaling pathways for TF induction differ from those of other LPS-responsive monocyte/macrophage gene products. Thus, this study documents specific modulation of the expression of LPS-inducible genes in monocytic cells by oxLDL. Factors that enhance TF expression in monocyte/macrophage cells present in atheroma may contribute to the severity of thrombotic episodes and complications observed in atherosclerosis.
Brand
K
K
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Banka
C L
CL
Mackman
N
N
Terkeltaub
R A
RA
Fan
S T
ST
Curtiss
L K
LK
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D010084:Oxidation-Reduction; D013925:Thromboplastin / Q000096:biosynthesis*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016209:Interleukin-8; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin