oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21.

oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21.
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DOI:
10.1155/2012/320953
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发表时间:
2012
影响因子:
4.6
通讯作者:
Weis M
Weis M
中科院分区:
医学3区
文献类型:
--
作者:
Nickel T;Pfeiler S;Summo C;Kopp R;Meimarakis G;Sicic Z;Lambert M;Lackermair K;David R;Beiras-Fernandez A;Kaczmarek I;Weis M

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介绍。树突状细胞(dc)和oxLDL在动脉粥样硬化过程中发挥重要作用,在斑块进展过程中dc在斑块中积累。我们的目的是研究oxLDL在调节DC归巢受体CCR7和内皮配体CCL21中的作用。方法与结果。采用qRT-PCR和免疫荧光技术检测了47例动脉粥样硬化性颈动脉斑块中DC归巢受体CCR7及其内皮配体CCL21的表达。在体外,我们研究了CCR7在dc和CCL21在人微血管内皮细胞(HMECs)上的表达对oxLDL的响应。与非动脉粥样硬化对照组相比,动脉粥样硬化斑块中CCL21-和CCR7- mrna水平显著下调[CCL21为90%,CCR7为81% (P < 0.01)]。在体外,oxLDL使dc上的CCR7 mRNA水平降低30%,蛋白质水平降低46%。此外,oxLDL显著降低HMECs CCL21 mRNA表达量50% (P < 0.05),降低蛋白表达量24% (P < 0.05)。结论。DC在动脉粥样硬化斑块中的积累似乎与趋化因子及其配体的下调有关,而趋化因子及其配体可以调节DC的迁移。oxLDL诱导CCR7和CCL21的体外下调,这可能在减少DC从斑块迁移中发挥作用。
Introduction. Dendritic cells (DCs) and oxLDL play an important role in the atherosclerotic process with DCs accumulating in the plaques during plaque progression. Our aim was to investigate the role of oxLDL in the modulation of the DC homing-receptor CCR7 and endothelial-ligand CCL21. Methods and Results. The expression of the DC homing-receptor CCR7 and its endothelial-ligand CCL21 was examined on atherosclerotic carotic plaques of 47 patients via qRT-PCR and immunofluorescence. In vitro, we studied the expression of CCR7 on DCs and CCL21 on human microvascular endothelial cells (HMECs) in response to oxLDL. CCL21- and CCR7-mRNA levels were significantly downregulated in atherosclerotic plaques versus non-atherosclerotic controls [90% for CCL21 and 81% for CCR7 (P < 0.01)]. In vitro, oxLDL reduced CCR7 mRNA levels on DCs by 30% and protein levels by 46%. Furthermore, mRNA expression of CCL21 was significantly reduced by 50% (P < 0.05) and protein expression by 24% in HMECs by oxLDL (P < 0.05). Conclusions. The accumulation of DCs in atherosclerotic plaques appears to be related to a downregulation of chemokines and their ligands, which are known to regulate DC migration. oxLDL induces an in vitro downregulation of CCR7 and CCL21, which may play a role in the reduction of DC migration from the plaques.
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