Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide.
Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide.
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DOI：
10.1186/1742-2094-8-21
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发表时间：
2011-03-03
影响因子：
9.3
通讯作者：
Garcia-Segura LM
中科院分区：
文献类型：
--
作者：
Bellini MJ;Hereñú CB;Goya RG;Garcia-Segura LM
胰岛素样生长因子-I（IGF-I）在中枢神经系统中发挥神经保护作用，其至少部分通过控制星形胶质细胞的活化来介导。在这项研究中，我们评估了外源性IGF-I和IGF-I基因治疗在减少大脑皮层星形胶质细胞炎症反应中的疗效。携带大鼠IGF-I基因的腺病毒载体和携带编码单纯疱疹病毒1型胸苷激酶的杂合基因的对照腺病毒载体与维多利亚水母增强型绿色荧光蛋白融合用于本研究。将来自小鼠大脑皮层的原代星形胶质细胞与媒介物、IGF-I、IGF-I腺病毒载体或对照载体孵育24小时或72小时;并暴露于细菌脂多糖以诱导炎症反应。用放射免疫法测定IGF-I水平。采用实时荧光定量聚合酶链反应（RT-PCR）检测IL-6、TNF-α、IL-1β和Toll样受体4 mRNA水平。通过蛋白质印迹法评估IGF-I受体和IGF结合蛋白2和3的水平。免疫细胞化学法检测核因子κB（p65）的亚细胞分布。通过单因素方差分析，然后进行Bonferroni pot hoc检验评估统计学显著性。IGF-I基因治疗增加IGF-I水平，而不影响IGF-I受体或IGF结合蛋白。外源性IGF-I和IGF-I基因治疗降低了Toll样受体4的表达，抵消了脂多糖诱导的星形胶质细胞炎症反应。此外，IGF-I基因治疗减少了脂多糖诱导的核因子κB（p65）向细胞核的移位。这些发现证明了外源性IGF-I和IGF-I基因治疗在减少星形胶质细胞的炎症反应中的功效。IGF-I基因治疗可能代表一种新的方法，以减少神经胶质细胞的炎症反应。
Insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central nervous system that are mediated at least in part by control of activation of astrocytes. In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy in reducing the inflammatory response of astrocytes from cerebral cortex. An adenoviral vector harboring the rat IGF-I gene and a control adenoviral vector harboring a hybrid gene encoding the herpes simplex virus type 1 thymidine kinase fused to Aequorea victoria enhanced green fluorescent protein were used in this study. Primary astrocytes from mice cerebral cortex were incubated for 24 h or 72 h with vehicle, IGF-I, the IGF-I adenoviral vector, or control vector; and exposed to bacterial lipopolysaccharide to induce an inflammatory response. IGF-I levels were measured by radioimmunoassay. Levels of interleukin 6, tumor necrosis factor-α, interleukin-1β and toll-like receptor 4 mRNA were assessed by quantitative real-time polymerase chain reaction. Levels of IGF-I receptor and IGF binding proteins 2 and 3 were assessed by western blotting. The subcellular distribution of nuclear factor κB (p65) was assessed by immunocytochemistry. Statistical significance was assessed by one way analysis of variance followed by the Bonferroni pot hoc test. IGF-I gene therapy increased IGF-I levels without affecting IGF-I receptors or IGF binding proteins. Exogenous IGF-I, and IGF-I gene therapy, decreased expression of toll-like receptor 4 and counteracted the lipopolysaccharide-induced inflammatory response of astrocytes. In addition, IGF-I gene therapy decreased lipopolysaccharide-induced translocation of nuclear factor κB (p65) to the cell nucleus. These findings demonstrate efficacy of exogenous IGF-I and of IGF-I gene therapy in reducing the inflammatory response of astrocytes. IGF-I gene therapy may represent a new approach to reduce inflammatory reactions in glial cells.
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影响因子：
7.4
作者：
Kipp, Markus;Karakaya, Serkan;Beyer, Cordian
通讯作者：
Beyer, Cordian
影响因子：
3.3
作者：
Herenu, C. B.;Sonntag, W. E.;Morel, G. R.;Portiansky, E. L.;Goya, R. G.
通讯作者：
Goya, R. G.
影响因子：
6.2
作者：
Cerciat, M.;Unkila, M.;Arevalo, M. -A.
通讯作者：
Arevalo, M. -A.
影响因子：
3.7
作者：
Arimilli, Subhashini;Johnson, John B.;Parks, Griffith D.
通讯作者：
Parks, Griffith D.
影响因子：
5.1
作者：
Herenu, C. B.;Cristina, C.;Goya, R. G.
通讯作者：
Goya, R. G.