NEUROTROPHIC ACTIVITY OF CYTOKINE-ACTIVATED ASTROCYTES

细胞因子激活星形胶质细胞的神经营养活性

基本信息

批准号：
05671183
负责人：
YOSHIDA Kazunari
金额：
$ 1.41万
依托单位：
SCHOOL OF MEDICINE,KEIO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671183/
关键词：
neurotrophic factor astrocyte cytokine neural regeneration astrocyte nerve growth factor cytokine neurotrophic factor cholinergic neuron interleukin-1 tumer necresis factor fibroblaot growth factor 神経成長因子線維芽細胞成長因子インターロイキン-1 /

项目摘要

1. Nerve growth kfactor (NGF) and non-NGF-type neurotrophic activities have been found to accumulate transiently in cerebrospinal fluid following surgery. These neurotrophic activites are probably important in the regeneration of damaged neural networks in the central nervous system.2. A novel neurotrophoc factor which enhances choline acetyltranferase activity of brainstem cholinergic neurons has been shown to exist in astrocyte-conditioned medium. Cytokines such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and acidic fibroblast growth factor (aFGF) increased an amount of the factor released from astrocytes. The factor was revealed to be a heparin-binding protein with a molecular weight of 40-60 kD.3. Three isoforms (18,22 and 24 kD) of basic fibroblast growth factor (bFGF) are known to be expressed in astrocytes. We have shown that the expression of 22,24-kD isoforms but not of 18-kD isoform in astrocytes is enhanced by cytokines such as IL-1beta, TNF-alph … More a and epidermal growth factor (EGF), and that the bFGF content in the cytoplasm of astrocytes is initially ncreased by these cytokines followed by nuclear targeting and localization. In addition, 22-kD isoform has been shown to be released from astrocytes.4. We have demonstrated that ciliary neurotrophic factor (CNTF) can be released from astrocytes, and that cytokines such as IL-1beta, TNF-alpha and EGF increase CNTF release kfrom astrocytes.5. Transkforming growth factor-beta1 (TGF-beta1) has been shown to enhance the expression of neural cell adhesion molecule (NCAM) on astrocytes.These results indicate that as trocytes secrete various neurkotrophicfactors including a novel non-NGF-type neurotrophic factor (s) and so-called non-secretory factors such as bFGF and CNTF,and that the cytokines, which are lilely to be present in the brain following injury, may play an important role in the repair of damaged neunal networks by increasing the expression or release of these neurotrophic factors and cell adhesion molecules by astrocytes Less

1。神经生长KFACTOR（NGF）和非NGF型神经营养活性在手术后在脑脊液中瞬时积累。这些神经营养活性在中枢神经系统中受损神经元的再生可能很重要。2。一种新型的神经营养因子，增强了脑干胆碱能神经元的胆碱乙酰基转叶酶活性，已显示在星形胶质细胞调节培养基中。细胞因子（例如白介素1Beta（IL-1BETA），肿瘤坏死因子-Alpha（TNF-Alpha）和酸性成纤维细胞生长因子（AFGF）增加了从星形胶质细胞释放的因子的数量。该因子揭示为一种肝素结合蛋白，分子量为40-60 kD.3。已知在星形胶质细胞中表达了三种基本成纤维细胞生长因子（BFGF）的三种同工型（18,22和24 kd）。我们已经表明，星形胶质细胞中22,24-kD同工型的表达并非由IL-1BETA，TNF-ALPH等细胞因子增强，而tnf-alph的细胞因子（EGF）（EGF）的表达不断增强，并且由核细胞中的BFGF含量进行了核心量，并由这些核心群体进行了改善。此外，已显示22 kD同工型从星形胶质细胞释放。4。我们已经证明，睫状神经营养因子（CNTF）可以从星形胶质细胞中释放出来，并且诸如IL-1Beta，TNF-Alpha和EGF之类的细胞因子会增加CNTF释放CNTF的CNTF kntrom星形胶质细胞。5。已证明转化生长因子-BETA1（TGF-BETA1）可以增强星形胶质细胞上神经元细胞粘附分子（NCAM）的表达。这些结果表明，随着小核细胞的秘密各种神经营养因子，包括一种新型的非NGF型神经营养因子（S）和所谓的非分泌因子，例如BFGFF和CNTF，以及细胞因子，以及细胞因子，这些因子在受伤后可能会在大脑中表现出来的重要性，并且在疾病中可能会在大脑中表现出重要的作用，并在疾病中释放出重要的因素，并在疾病中起作用，并在这些因素上起作用。星形胶质细胞较少的细胞粘合剂分子