Fibroblast growth factors stimulate nerve growth factor synthesis and secretion by astrocytes

Nerve growth factor (NGF) is produced and secreted by astrocytes and fibroblasts, but not by microglia, in a primary non-neuronal cell culture derived from newborn rat brains under a standard culture condition. NGF secretion by astrocytes was highest just after passage and then gradually decreased. There is no significant difference in NGF secretion by astrocytes from five sites of origin tested: cerebral cortex, striatum, hippocampus, septum, and cerebellum. Acidic and basic fibroblast growth factors (aFGF and bFGF) significantly increased NGF secretion by astrocytes. The effect of aFGF was greater than that of bFGF, and the effect of both FGFs was not additive at the maximum concentration. The peak of NGF secretion stimulated by aFGF occurred 3-12 h after the addition of aFGF. On the other hand, the dramatic increase in cell numbers was observed 12-48 h after stimulation, and the morphological change became significant 24 h after aFGF stimulation. NGF synthesized by astrocytes is rapidly secreted into the culture medium and aFGF enhances NGF secretion from the transcription level, because cycloheximide and actinomycin-D completely inhibited NGF secretion by astrocytes in the presence or absence of aFGF. Epidermal growth factor (EGF), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) also increased NGF secretion by astrocytes to a certain extent. NGF secretion by astrocytes in the presence of a maximum dose of aFGF was enhanced by the addition of IL-1 beta or TNF-alpha, but not EGF. However, platelet-derived growth factor, interleukin-3, and interleukin-6 had no significant effects. FGFs also enhanced NGF secretion by fibroblasts derived from meninges, but not by microglia.