Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis.
Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis.
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DOI：
10.1186/1471-2172-8-10
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发表时间：
2007-07-16
期刊：
影响因子：
3
通讯作者：
Tsirka SE
中科院分区：
文献类型：
--
作者：
Bhasin M;Wu M;Tsirka SE
髓鞘少突胶质细胞糖蛋白（MOG）诱导的实验性自身免疫性脑脊髓炎（EAE）是多发性硬化症（MS）最常用的小鼠模型。在EAE的进展过程中，小胶质细胞，大脑的免疫活性细胞，变得活化并聚集在脱髓鞘病变周围。小胶质细胞活化由细胞外蛋白酶组织纤溶酶原激活物（tPA）介导，缺乏tPA的小鼠显示改变的EAE进展。在这项研究中，我们已经使用了药理学抑制剂和刺激剂的小胶质细胞/巨噬细胞激活，以检查EAE进展中的小胶质细胞激活的时间要求，并确定这种方法是否可能具有治疗价值。使用三肽巨噬细胞/小胶质细胞抑制因子MIF（TKP）和四肽巨噬细胞/小胶质细胞刺激因子tuftsin（TKPR）的干预减轻了EAE症状，并显示巨噬细胞/小胶质细胞激活的时机对EAE的临床结果至关重要。我们表明，通过改变小胶质细胞激活的时间，可以在早期有利地操纵疾病进展，这反过来又改变了全身免疫反应，有利于上调T辅助细胞2基因，促进EAE的恢复。巨噬细胞/小胶质细胞活性的预防性和治疗性调节显著改变了EAE在症状阶段的结果。已经确定了代表治疗和预防MS的潜在探索途径的特定分子靶点。
Myelin Oligodendrocyte Glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is the most commonly used mouse model for multiple sclerosis (MS). During the of progression of EAE, microglia, the immunocompetent cells of the brain, become activated and accumulate around demyelinated lesions. Microglial activation is mediated by the extracellular protease tissue Plasminogen Activator (tPA), and mice lacking tPA display altered EAE progression. In this study, we have used pharmacological inhibitors and stimulators of microglial/macrophage activation to examine the temporal requirement for microglial activation in EAE progression and to determine whether such approaches might potentially be of therapeutic value. Intervention using the tripeptide macrophage/microglia inhibitory factor MIF (TKP) and the tetrapeptide macrophage/microglial stimulator tuftsin (TKPR) attenuated EAE symptoms and revealed that the timing of macrophage/microglial activation is critical for the clinical outcome of EAE. We show that the disease progression can potentially be manipulated favorably at early stages by altering the timing of microglial activation, which in turn alters the systemic immune response to favor upregulation of T helper cell 2 genes that promote recovery from EAE. Preventative and therapeutic modulation of macrophage/microglial activity significantly alters the outcome of EAE at symptomatic stages. Specific molecular targets have been identified that represent potential avenues of exploration for the treatment and prevention of MS.
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影响因子：
9.2
作者：
Rogove, AD;Tsirka, SE
通讯作者：
Tsirka, SE
影响因子：
5.4
作者：
HUITINGA, I;DAMOISEAUX, JGMC;DIJKSTRA, CD
通讯作者：
DIJKSTRA, CD
影响因子：
3.5
作者：
AURIAULT, C;JOSEPH, M;CAPRON, A
通讯作者：
CAPRON, A
影响因子：
3.3
作者：
CONSTANTINESCU, CS;VENTURA, E;ROSTAMI, A
通讯作者：
ROSTAMI, A
影响因子：
2.4
作者：
Gage, JR;Fonarow, G;Vredevoe, DL
通讯作者：
Vredevoe, DL