Mix Eilhard, Ibrahim Saleh M, Pahnke Jens, Glass Anne, Mazón-Peláez Ignacio, Lemcke Susanne, Koczan Dirk, Gimsa Ulrike, Bansemer Sven, Scheel Thomas, Karopka Thomas, Böttcher Tobias, Müller Jana, Dazert Eike, Antipova Veronica, Hoffrogge Raimund, Wree Andreas, Zschiesche Marlies, Strauss Ulf, Kundt Günther, Warzok Rolf, Gierl Lothar, Rolfs Arndt
Department of Neurology, University of Rostock, Gehlsheimer Str. 20, D-18147 Rostock, Germany.
J Autoimmun. 2006 Dec;27(4):251-65. doi: 10.1016/j.jaut.2006.09.006. Epub 2006 Nov 3.
The effect of Atorvastatin on transcriptional activity in murine experimental autoimmune encephalomyelitis (EAE) induced by PLP peptide 139-151 was analyzed by DNA microarray technique in lymph nodes and spinal cord at onset (10 days), height (20 days) and first remission (30 days) of disease. Fourteen genes were selectively influenced by Atorvastatin in EAE mice. They are mainly related to immune cell functions and regulation of cell-to-cell interaction. Interestingly, seven genes were also differentially regulated in CFA-injected control mice. But qualitative and quantitative differences to EAE mice argue for a dependency of statin effects on the activation status of target cells. Differential regulation of the newly detected candidate genes of statin effects COX-1 and HSP-105 and the previously known statin-responsive genes ICAM-1 and CD86 was confirmed by Western blot and immunohistochemistry. Flow cytometric analysis of lymph node cells revealed that the effect of Atorvastatin treatment in non-immunized healthy animals resembled the effect of immunization with PLP peptide regarding changes of T helper cells, activated B cells and macrophages. In EAE mice, these effects were partially reversed by Atorvastatin treatment. Monitoring of expression of the newly identified candidate genes and patterns of lymphocyte subpopulations might predict the responsiveness of multiple sclerosis patients to statin treatment.
采用DNA微阵列技术，分析了阿托伐他汀对由PLP肽139 - 151诱导的小鼠实验性自身免疫性脑脊髓炎（EAE）在疾病发作期（10天）、高峰期（20天）和首次缓解期（30天）时淋巴结和脊髓中转录活性的影响。在EAE小鼠中，有14个基因受到阿托伐他汀的选择性影响。它们主要与免疫细胞功能以及细胞间相互作用的调节有关。有趣的是，在注射完全弗氏佐剂（CFA）的对照小鼠中，也有7个基因受到差异调节。但与EAE小鼠在定性和定量上的差异表明，他汀类药物的作用依赖于靶细胞的激活状态。通过蛋白质免疫印迹法和免疫组织化学法证实了新检测到的他汀类药物作用候选基因COX - 1和HSP - 105以及先前已知的他汀类药物反应基因ICAM - 1和CD86的差异调节。对淋巴结细胞的流式细胞术分析显示，在未免疫的健康动物中，阿托伐他汀治疗的效果在T辅助细胞、活化B细胞和巨噬细胞变化方面类似于用PLP肽免疫的效果。在EAE小鼠中，这些效果通过阿托伐他汀治疗得到部分逆转。监测新鉴定的候选基因的表达以及淋巴细胞亚群的模式可能预测多发性硬化症患者对他汀类药物治疗的反应性。
