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A peripheral nerve reproduction control structure by one oxidized form galectin-1 instruction macrophage.

一种由氧化型半乳糖凝集素-1指令巨噬细胞控制周围神经再生的结构。

基本信息

批准号：
17500265
负责人：
HORIE Hidenori
金额：
$ 2.24万
依托单位：
Kanagawa Dental College (2006)Waseda University (2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Oxidized galectin-1 (GAL-1/0x) stimulates macrophages to promote axonal regeneration in peripheral nerves after nerve injury. But, the mechanism of GAL-1/0x, how to regulate macrophages, remains to be clarified. Here we demonstrated effects of GAL-/Ox on mRNA expression of four injury related molecules, interleukin-1β (IL-1β), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and inducible NO synthase (iNOS) in cultured rat peritoneal macrophages. RT-PCR analysis revealed that IL-6 as well as iNOS mRNA expressions were up-regulated by the treatment with 1 ng/ml GAL-1/0x, but the other mRNA did not show significant differences by the application of GAL-1/0x. Increased IL-6 may promote axonal regeneration in peripheral nerves, but up-regulated iNOS, promoting oxidization, may damage regenerating nerves. This problem was resolved by the following experiments. Using lipopolysaccharide (LPS) is one of the typical substance to stimulate macrophages to promote mRNA expressions of cytoki … More nes and iNOS. When 10 to 100 ng/ml LPS was applied to cultured macrophages, mRNA expressions of IL-1β, IL-6, LIF, and iNOS were up-regulated. The treatment of 1 ng/ml GAL-1/0x reduced their expressions. This inhibition by GAL-1/0x treatment reduced with decreasing its concentration to 0.1 ng/ml and 0.01 ng/ml GAL-1/0x showed no significant inhibitory effect. These results indicate the possibility that GAL-1/0x regulates expressions of IL-1β, IL-6, LIF, and iNOS to a suitable level, otherwise damaging injured tissues in an excess. Since it has been proved that galectin-1 locates as a reduced form in neurons, their axons, and Schwann cells in injured peripheral nerves and is secreted into extra-cellular space to change into oxidized galectin-1 after oxidization, GAL-1/0x may restrict macrophages to secrete the factors in a proper amount resulting with the promotion of recovery. Since GAL-1/0x, macrophage, and LPS are commonly seen in general inflammation, GAL-1/0x is expected to improve inflammation. Less

氧化半乳糖凝集素-1（GAL-1/0x）刺激巨噬细胞促进神经损伤后周围神经轴突再生。但GAL-1/0x对巨噬细胞的调节机制尚不清楚。在此，我们证明了GAL-/Ox对培养的大鼠腹腔巨噬细胞中四种损伤相关分子，白细胞介素-1 β（IL-1β）、白细胞介素-6（IL-6）、白血病抑制因子（LIF）和诱导型一氧化氮合酶（iNOS）mRNA表达的影响。RT-PCR分析显示，IL-6和iNOSmRNA的表达在1 ng/ml GAL-1/0x处理后均显著上调，而其他mRNA的表达在GAL-1/0x处理后无显著差异。增加IL-6可促进周围神经轴突再生，但上调iNOS，促进氧化，可能会损害再生神经。通过以下实验解决了这个问题。脂多糖（lipopolysaccharide，LPS）是刺激巨噬细胞促进细胞因子mRNA表达的典型物质之一。 ...更多信息内斯和iNOS。10 ~ 100 ng/ml LPS作用于培养的巨噬细胞后，IL-1β、IL-6、LIF和iNOS的mRNA表达上调。1 ng/ml GAL-1/OX处理降低了它们的表达。GAL-1/Ox处理的这种抑制随着其浓度降低至0.1 ng/ml而降低，并且0.01 ng/ml GAL-1/Ox显示无显著抑制作用。这些结果表明GAL-1/OX可能将IL-1β、IL-6、LIF和iNOS的表达调节至合适的水平，否则会过度损伤损伤组织。由于已经证明Galectin-1在受损的周围神经中以还原形式存在于神经元及其轴突和雪旺细胞中，并在氧化后分泌到细胞外空间以转变为氧化的Galectin-1，GAL-1/OX可以限制巨噬细胞分泌适量的因子，从而促进恢复。由于GAL-1/0x、巨噬细胞和LPS在一般炎症中常见，因此预期GAL-1/0x可改善炎症。少