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

• 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 /

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. 神经生长因子（NGF）和非NGF型神经营养活动被发现在手术后脑脊液中短暂积累。这些神经营养活动可能在中枢神经系统受损神经网络的再生中起重要作用。星形胶质细胞条件培养基中存在一种新的神经营养因子，可增强脑干胆碱能神经元的胆碱乙酰转移酶活性。白细胞介素-1 β (il -1 β)、肿瘤坏死因子- α (tnf - α)和酸性成纤维细胞生长因子（aFGF）等细胞因子增加了星形胶质细胞释放的该因子的量。该因子是一种分子量为40- 60kd的肝素结合蛋白。碱性成纤维细胞生长因子（bFGF）的三种亚型（18、22和24 kD）已知在星形胶质细胞中表达。我们发现，星形胶质细胞中22,24- kd异构体而非18-kD异构体的表达可被il -1 β、tnf - α和表皮生长因子（EGF）等细胞因子增强，并且星形胶质细胞细胞质中的bFGF含量最初是由这些细胞因子增加的，然后是核靶向和定位。此外，22-kD异构体已被证实从星形胶质细胞中释放。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，并且细胞因子如il -1 β、tnf - α和EGF可以增加星形胶质细胞中CNTF的释放。转化生长因子- β 1 （tgf - β 1）可增强星形胶质细胞上神经细胞粘附分子（NCAM）的表达。这些结果表明，由于胶质细胞分泌各种神经营养因子，包括一种新型的非ngf型神经营养因子和所谓的非分泌因子，如bFGF和CNTF，而这些细胞因子可能在损伤后的大脑中存在，通过增加星形胶质细胞对这些神经营养因子和细胞粘附分子的表达或释放，在受损神经网络的修复中发挥重要作用

项目成果

吉田一成: "サイトカインにより活性化されるアストロサイトの神経栄養効果に及ぼすglucocorticoidの作用" 神経組織の再生・成長・移植. 5. 13-14 (1993)

Kazunari Yoshida：“糖皮质激素对细胞因子激活的星形胶质细胞的神经营养作用的影响”神经组织的再生、生长和移植。5. 13-14 (1993)

吉田一成: "サイトカイン,glucocorticordによるアストロサイトのNGF,NCAM発現調節" 神経化学. 32. 412-413 (1993)

Kazunari Yoshida：“细胞因子糖皮质激素对星形胶质细胞中 NGF 和 NCAM 表达的调节”《神经化学》32. 412-413 (1993)。

Kamiguchi H,Yoshida K,Sagoh M,Sasaki H,Inaba M,Wakamoto H,Otani M,Toya S.: "Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines." Neurochem Res. 20. 1187-1193 (1995)

Kamiguchi H、Yoshida K、Sagoh M、Sasaki H、Inaba M、Wakamoto H、Otani M、Toya S.：“培养的星形胶质细胞中睫状神经营养因子的释放及其细胞因子的调节。”

Hiroyuki Kamiguchi et al: "Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines" Neurochem Res. 20. 1187-1193 (1995)

Hiroyuki Kamiguchi 等人：“培养的星形胶质细胞释放睫状神经营养因子及其通过细胞因子的调节”Neurochem Res。

Kamiguchi H,Yoshida K,Shimazaki K,Inaba M,Sasaki H,Kagami H,Otani M,Toya S: "Effects of cytokines on the expression of bFGF isoforms and their subcellular Iocalization in cultured astrocytes." Jpn Soc Neural GRT. (in press).

Kamiguchi H、Yoshida K、Shimazaki K、Inaba M、Sasaki H、Kagami H、Otani M、Toya S：“细胞因子对培养的星形胶质细胞中 bFGF 亚型表达及其亚细胞定位的影响。”