Human monocytes/macrophages release TNF-alpha in response to Ox-LDL

被引:179
|
作者
Jovinge, S
Ares, MPS
Kallin, B
Nilsson, J
机构
[1] Department of Medicine, Karolinska Hospital, King Gustaf Vth Research Institute, Stockholm
[2] King Gustaf Vth Research Institute, Karolinska Hospital
关键词
atherosclerosis; oxidized LDL; smooth muscle cells; tumor necrosis factor-alpha; AP-1;
D O I
10.1161/01.ATV.16.12.1573
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The uptake of oxidatively modified low density lipoprotein (Ox-LDL) by intimal macrophages is believed to play a key role in the development of atherosclerosis. The present study demonstrates that Ox-LDL in low concentrations activates monocyte/macrophage release of factors that stimulate smooth muscle cell growth, whereas higher concentrations are inhibitory. Exposure of monocytes/macrophages to 8 mu g/mL Ox-LDL increased expression of tumor necrosis factor-alpha (TNF-alpha) mRNA but had no effect on interleukin-1 beta, platelet-derived growth factor B and heparin-binding epidermal growth factor-like mitogen mRNA levels. Ox-LDL also stimulated monocyte/macrophage release of TNF-alpha in a dose-dependent manner, with maximal effect at an LDL concentration of 8 mu g/mL. Addition of TNF-alpha-blocking antibodies to conditioned medium from monocytes/macrophages already exposed to Ox-LDL reduced mitogenic activity by 44.7 +/- 8.4% (P < .005). Stimulation of TNF-alpha release by Ox-LDL was associated with activation of transcription factor AP-1, whereas the activity of transcription factor nuclear factor-kappa B remained unchanged. These findings suggest that enhanced secretion of TNF-alpha by macrophages exposed to Ox-LDL may be involved in the formation of atherosclerotic lesions.
引用
收藏
页码:1573 / 1579
页数:7
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