NEUROTROPHIC ACTIVITY OF CYTOKINE-ACTIVATED ASTROCYTES

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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