Inhibition of lipopolysaccharide-induced inflammatory responses by an apolipoprotein AI mimetic peptide
Inhibition of lipopolysaccharide-induced inflammatory responses by an apolipoprotein AI mimetic peptide
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DOI：
10.1161/01.res.0000176530.66400.48
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发表时间：
2005-08-05
影响因子：
20.1
通讯作者：
White, CR
中科院分区：
文献类型：
--
作者：
Gupta, H;Dai, LJ;White, CR
以往的研究表明，高密度脂蛋白和载脂蛋白AI抑制脂多糖（LPS）诱导的炎症反应。本研究的目的是检验apoAI模拟肽L-4F发挥与apoAI类似的抑制作用的假设。LPS预处理人脐静脉内皮细胞（HUVECs）可诱导THP-1单核细胞粘附。用LPS和L-4F（1至50 μ g/mL）孵育细胞以浓度依赖性方式降低THP-1粘附。这种反应与细胞因子、趋化因子和粘附分子的合成显著减少有关。L-4F降低LPS或脂质A诱导的血管细胞粘附分子-1的表达，而对照肽（Sc-4F）则无影响。与LPS处理相反，L-4F不抑制IL-1 β或肿瘤坏死因子-α诱导的血管细胞粘附分子-1表达。L-4F对LPS诱导炎症标志物的抑制作用与LPS与其血浆载体分子脂多糖结合蛋白的结合减少以及LPS与HUVEC单层的结合减少有关。HUVEC培养液中的LPS和L-4F通过快速蛋白液相色谱法分离，并定位于相同的组分，表明这些分子之间的物理相互作用。对LPS的促炎反应与脂质A与细胞表面受体的结合有关。目前的研究表明，L-4F减少LPS和脂质A诱导的炎症标志物的表达，并表明apoAI肽模拟物可用于治疗与内毒素血症相关的炎症。
Previous studies suggest that high-density lipoprotein and apoAI inhibit lipopolysaccharide (LPS)-induced inflammatory responses. The goal of the current study was to test the hypothesis that the apoAI mimetic peptide L-4F exerts antiinflammatory effects similar to apoAI. Pretreatment of human umbilical vein endothelial cells (HUVECs) with LPS induced the adhesion of THP-1 monocytes. Incubation of cells with LPS and L-4F (1 to 50 mu g/mL) reduced THP-1 adhesion in a concentration-dependent manner. This response was associated with a significant reduction in the synthesis of cytokines, chemokines, and adhesion molecules. L-4F reduced vascular cell adhesion molecule-1 expression induced by LPS or lipid A, whereas a control peptide (Sc-4F) showed no effect. In contrast to LPS treatment, L-4F did not inhibit IL-1 beta- or tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression. The inhibitory effect of L-4F on LPS induction of inflammatory markers was associated with reduced binding of LPS to its plasma carrier molecule, lipopolysaccharide binding protein, and decreased binding of LPS to HUVEC monolayers. LPS and L-4F in HUVEC culture medium were fractionated by fast protein liquid chromatography and were localized to the same fractions, suggesting a physical interaction between these molecules. Proinflammatory responses to LPS are associated with the binding of lipid A to cell surface receptors. The current studies demonstrate that L-4F reduces the expression of inflammatory markers induced by LPS and lipid A and suggest that apoAI peptide mimetics may be useful in the treatment of inflammation associated with endotoxemia.