Effects of Oxidatively Modified Low Density Lipoprotein on NFkB Activation

Document Type

Article

Publication Date

12-1-1997

Description

Oxidatively modified low density lipoprotein (OM-LDL) is believed to influence the gene expression in macrophage during atherogenesis. We report here that OM-LDL altered the NF-kB activity in RAW264.7 macrophage. Human LDL was oxidized by an azo-initiator, azobis-2-amidinopropane HCI. In the absence of OM-LDL, RAW264.7 macrophage expressed low levels of NFkB (p50/p65) and p50/p50. Lipopolysaccharide (LPS) treatment lead to the high level activation of p50/p65 in macrophage, while the p50/p50 remained unchange. However, by treating macrophage with OM-LDL, p50/p65 was selectively suppressed and p50/p50 was slightly activated. In LPS stimulated macrophage, OM-LDL slightly suppressed the activation of p50/p65 but did not significantly activate p50/p50. Further experiments showed that nitric oxide (NO) production in macrophage was stimulated by LPS. OM-LDL suppressed the NO production caused by LPS. These results indicate that OM-LDL may suppress the expression of NFkB regulated genes such as NO synthetase by the activation of p50/50 homodimer, which may act to suppress transcription factor p50/p65.

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