Salazar Giulia, Bellocchi Chiara, Todoerti Katia, Saporiti Federica, Piacentini Luca, Scorza Raffaella, Colombo Gualtiero I
Referral Centre for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
Referral Centre for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
Eur J Pharmacol. 2016 Jul 5;782:59-69. doi: 10.1016/j.ejphar.2016.04.018. Epub 2016 Apr 12.
Aminaphtone, a drug used in the treatment of chronic venous insufficiency (CVI), showed a remarkable role in the modulation of several vasoactive factors, like endothelin-1 and adhesion molecules. We analysed in vitro the effects of Aminaphtone on whole-genome gene expression and production of different inflammatory proteins. ECV-304 endothelial cells were stimulated with IL-1β 100U/ml in the presence or absence of Aminaphtone 6μg/ml. Gene expression profiles were compared at 1, 3, and 6h after stimulation by microarray. Supernatants of ECV-304 cultures were analysed at 3, 6, 12, and 24h by multiplex ELISA for production of several cytokine and chemokines. Microarrays showed a significant down-regulation at all times of a wide range of inflammatory genes. Aminaphtone appeared also able to modulate the regulation of immune response process (down-regulating cytokine biosynthesis, transcripts involved in lymphocyte differentiation and cell proliferation, and cytokine-cytokine receptor interaction) and to regulate genes engaged in homeostasis, secretion, body fluid levels, response to hypoxia, cell division, and cell-to-cell communication and signalling. Results were confirmed and extended analysing the secretome, which showed significant reduction of the release of 14 cytokines and chemokines. These effects are predicted to be mediated by interaction with different transcription factors. Aminaphtone was able to modulate the expression of inflammatory molecules relevant to the pathogenesis of several conditions in which the endothelial dysfunction is the main player and early event, like scleroderma, lung fibrosis, or atherosclerosis.
氨萘普汀是一种用于治疗慢性静脉功能不全（CVI）的药物，在调节多种血管活性因子（如内皮素-1和黏附分子）方面发挥着显著作用。我们在体外分析了氨萘普汀对全基因组基因表达和不同炎症蛋白产生的影响。在存在或不存在6μg/ml氨萘普汀的情况下，用100U/ml的IL-1β刺激ECV-304内皮细胞。通过微阵列在刺激后1、3和6小时比较基因表达谱。通过多重ELISA在3、6、12和24小时分析ECV-304培养物的上清液中几种细胞因子和趋化因子的产生。微阵列显示，在所有时间点，多种炎症基因均有显著下调。氨萘普汀似乎还能够调节免疫反应过程的调节（下调细胞因子生物合成、参与淋巴细胞分化和细胞增殖的转录本以及细胞因子-细胞因子受体相互作用），并调节参与体内平衡、分泌、体液水平、对缺氧的反应、细胞分裂以及细胞间通讯和信号传导的基因。通过分析分泌组证实并扩展了结果，分泌组显示14种细胞因子和趋化因子的释放显著减少。预计这些作用是通过与不同转录因子的相互作用介导的。氨萘普汀能够调节与几种以内皮功能障碍为主要因素和早期事件（如硬皮病、肺纤维化或动脉粥样硬化）发病机制相关的炎症分子的表达。
