Neurotrophic Effects of Cytokine-activated Astrocytes.-Basic research for Elucidation of Interaction between Neuron and Glia, and Restoration of Damaged Neuronal Function-

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We have demonstrated that production and secretion of neurotrophic factors such as nerve growth factor (NGF) from astrocytes was enhanced by cytokines such as fibroblast growth factor(FGF), interleukin-1beta(IL-1beta), tumor necrosis factor-alpha(TNF-alpha), epidermal growth factor(EGF), transforming growth factor-beta1(TGF-beta1), which are likely to be present in the brain following injury.We have demonstrated new knowledge mentioned below, from 1996- to 1998.1. IL-1beta, TNF-alpha and EGF induced selective increase of high-molecular-weight bFGF isoforms in cultured rat hippocampal astrocytes.2. IL-1beta and TNF-alpha co-operatively enhanced a novel trophic activity of astrocytes for pontine cholinergic neurons.3. TGF-beta1 enhanced expression of NCAM in cultured rat hippocampal astrocytes.4. Hepatocyte growth factor(HGF) receptor, c-Met was expressed in cultured rat hippocampal astrocytes. Cytokines enhanced expression of c-Met protein in cultured rat hippocampal astrocytes.