Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland.
Inflammation. 2012 Aug;35(4):1567-84. doi: 10.1007/s10753-012-9472-3.
It is widely accepted that oxidized low-density lipoproteins and local infections or endotoxins in circulation contribute to chronic inflammatory process at all stages of atherosclerosis. The hallmark cells of atherosclerotic lesions-monocytes and macrophages-are able to detect and integrate complex signals derived from lipoproteins and pathogens, and respond with a spectrum of immunoregulatory cytokines. In this study, we show strong inhibitory effect of oxLDLs on anti-inflammatory interleukin-10 production by monocytes responding to TLR2 and TLR4 ligands. In contrast, pro-inflammatory tumor necrosis factor secretion was even slightly increased, when stimulated with lipopolysaccharide from Porphyromonas gingivalis-an oral pathogen associated with atherosclerosis. The oxLDLs modulatory activity may be explained by altered recognition of pathogen-associated molecular patterns, which involves serum proteins, particularly vitronectin. We also suggest an interaction between vitronectin receptor, CD11b, and TLR2. The presented data support a novel pathway for pathogen-accelerated atherosclerosis, which relies on oxidized low-density lipoprotein-mediated modulation of anti-inflammatory response to TLR ligands.
普遍认为，氧化型低密度脂蛋白和循环中的局部感染或内毒素在动脉粥样硬化的各个阶段都导致慢性炎症过程。动脉粥样硬化病变的标志性细胞——单核细胞和巨噬细胞——能够检测和整合来自脂蛋白和病原体的复杂信号，并通过一系列免疫调节细胞因子做出反应。在这项研究中，我们发现氧化型低密度脂蛋白对单核细胞对 TLR2 和 TLR4 配体的抗炎性白细胞介素 10 产生具有强烈的抑制作用。相比之下，当用牙龈卟啉单胞菌（一种与动脉粥样硬化相关的口腔病原体）的脂多糖刺激时，促炎性肿瘤坏死因子的分泌甚至略有增加。oxLDL 的调节活性可以通过改变对病原体相关分子模式的识别来解释，这涉及血清蛋白，特别是 vitronectin。我们还提出了 vitronectin 受体 CD11b 和 TLR2 之间的相互作用。所呈现的数据支持了一种新的病原体加速动脉粥样硬化的途径，该途径依赖于氧化型低密度脂蛋白介导的对 TLR 配体的抗炎反应的调节。
