Potteaux Stéphane, Deleuze Virginie, Merval Régine, Bureau Michel F, Esposito Bruno, Scherman Daniel, Tedgui Alain, Mallat Ziad
Centre de Recherche Cardiovasculaire Inserm Lariboisière, U689, Paris.
Eur Cytokine Netw. 2006 Mar;17(1):13-8.
Interleukin (IL)-10 has anti-atherogenic properties. However, the molecular mechanisms involved in IL-10 protection against atherosclerosis in vivo remain poorly understood. In this study, we examined the effect of IL-10 cDNA in vivo electrotransfer on diet-induced, endothelial activation.
C57BL/6J mice were fed an atherogenic diet for 10 days. Expression of VCAM-1 and ICAM-1 was examined in the aortic sinus, a region predisposed to atherogenesis in mice, using immunohistochemistry. NF-kappaB activation was examined using a monoclonal antibody that selectively reacts with the activated form of the p65 subunit.
We detected a low basal expression of activated NF-kappaB, VCAM-1 and ICAM-1 in the endothelium of the aortic sinus. Endothelial expression of activated NF-kappaB, VCAM-1 and ICAM-1 was markedly increased after 10 days on the atherogenic diet (p < 0.001). In vivo electrotransfer of a murine IL-10-encoding plasmid completely prevented diet-induced endothelial upregulation of activated NF-kappaB, VCAM-1 and ICAM-1 (p < 0.01).
In vivo electrotransfer of IL-10 cDNA prevents diet-induced endothelial activation. These results suggest that the protective effects of IL-10 may already occur in the very early stages of atherogenesis.
白细胞介素（IL）-10具有抗动脉粥样硬化特性。然而，IL-10在体内预防动脉粥样硬化的分子机制仍知之甚少。在本研究中，我们检测了IL-10 cDNA体内电转染对饮食诱导的内皮细胞活化的影响。
给C57BL/6J小鼠喂食致动脉粥样硬化饮食10天。使用免疫组织化学法检测小鼠易发生动脉粥样硬化的区域——主动脉窦中血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）的表达。使用与p65亚基活化形式选择性反应的单克隆抗体检测核因子κB（NF-κB）的活化情况。
我们检测到主动脉窦内皮中活化的NF-κB、VCAM-1和ICAM-1的基础表达较低。在致动脉粥样硬化饮食10天后，活化的NF-κB、VCAM-1和ICAM-1的内皮表达显著增加（p<0.001）。编码小鼠IL-10的质粒的体内电转染完全阻止了饮食诱导的活化NF-κB、VCAM-1和ICAM-1的内皮上调（p<0.01）。
IL-10 cDNA的体内电转染可预防饮食诱导的内皮细胞活化。这些结果表明，IL-10的保护作用可能在动脉粥样硬化的极早期就已出现。
