Oxidized low density lipoprotein inhibits lipopolysaccharide-induced binding of nuclear factor-kappa B to DNA and the subsequent expression of tumor necrosis factor-alpha and interleukin-1 beta in macrophages
Oxidized low density lipoprotein inhibits lipopolysaccharide-induced binding of nuclear factor-kappa B to DNA and the subsequent expression of tumor necrosis factor-alpha and interleukin-1 beta in macrophages
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DOI：
10.1172/jci118780
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发表时间：
1996-07-01
影响因子：
15.9
通讯作者：
Wiklund, O
中科院分区：
文献类型：
--
作者：
Ohlsson, BG;Englund, MCO;Wiklund, O
大量的证据表明氧化低密度脂蛋白（oxLDL）在动脉粥样硬化形成中起作用。我们研究了氧化低密度脂蛋白（oxLDL）和氧化甾醇对转录因子核因子（NF）-κ B（B）和AP-1与DNA结合的影响。这些转录因子参与了几种基因的调节，并在巨噬细胞活化过程中表达，例如内毒素（LPS）。氧化低密度脂蛋白不能诱导NF-κ B的结合，但氧化低密度脂蛋白预孵育后，LPS诱导的NF-κ B的反应显著降低。中等和高度氧化的低密度脂蛋白也降低AP-1的组成型DNA结合。因此，我们的数据表明oxLDL对AP-1的DNA结合的影响，这可能是由oxLDL的氧化固醇含量介导的。在暴露于LPS之前，在与oxLDL孵育的巨噬细胞中发现LPS诱导的TNF-α和IL-1 β mRNA和蛋白表达降低。这些观察结果表明，内化广泛氧化的LDL的巨噬细胞在其对炎症刺激的反应中受到抑制。
A large body of evidence suggests that oxidized LDL (oxLDL) has a role in atherogenesis. One effect is the impact on macrophage function, We have studied the effects of oxLDL and oxysterols on the binding of the transcription factors nuclear factor (NF)-kappa B and AP-1 to DNA, These transcription factors are involved in the regulation of several genes and expressed during activation of macrophages, for example by endotoxin (LPS). OxLDL did not induce binding of NF-KB, However, the LPS-induced response to NF-kappa B was substantially reduced after preincubation with oxLDL, Medium and highly oxidized LDL also decreased the constitutive DNA-binding of AP-1, Similar effects on AP-l-binding were seen with the oxysterols, 7 beta-hydroxycholesterol, 24-hydroxy-, 25-hydroxy-, and 27-hydroxy-cholesterol. Our data therefore suggest an effect of oxLDL on the DNA-binding of AP-1, which might be mediated by the oxysterol content of oxLDL. A decreased LPS-induced TNF-alpha and IL-1 beta mRNA and protein expression were found in macrophages incubated with oxLDL before LPS-exposure, These observations suggest that macrophages that internalize extensively oxidized LDL are suppressed in their response to inflammatory stimulation.