PMID- 1494917 OWN - NLM STAT- MEDLINE DCOM- 19920909 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 59 IP - 3 DP - 1992 Sep TI - Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts. PG - 919-31 AB - The neurotrophic activity of astrocytes and fibroblasts and its regulation by various cytokines were investigated. Astrocyte conditioned medium (ACM) enhanced the survival of neurons and the proliferation of astrocytes in embryonic cortical cultures grown in serum-free defined medium. However, these results were not affected by acidic fibroblast growth factor, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), and transforming growth factor-beta 1. In contrast, ACM induced choline acetyltransferase expression in septal cholinergic neurons via nerve growth factor (NGF)-dependent and -independent mechanisms. However, neither acidic nor basic fibroblast growth factor is involved in this biological activity in ACM. The cytokines listed above mainly stimulate NGF-mediated cholinergic neurotrophic activity in ACM. A combination of IL-1 beta and TNF alpha significantly enhanced choline acetyltransferase activity in septal neurons co-cultured with astrocytes, and this effect was found to be mediated by NGF produced by activated astrocytes. Effects of astrocytes on GABAergic neurons were also examined. ACM was found to increase glutamate decarboxylase activity in neuronal cultures from septum in the presence of Ara-C. However, the cytokines did not enhance this activity in ACM. Moreover, a combination of IL-1 beta and TNF alpha had no effect on glutamate decarboxylase activity in septal neurons co-cultured with astrocytes. In a final set of experiments, cholinergic neurotrophic activity in skin-derived fibroblast conditioned medium (FCM) was examined. FCM was found to possess biological activity similar to that of ACM on septal neurons grown in serum-free defined medium with Ara-C. The cytokines also enhanced NGF-mediated cholinergic neurotrophic activity in FCM. Astrocytes and fibroblasts were found to possess NGF-type and non-NGF-type cholinergic neurotrophic activity, and various cytokines were found to regulate the NGF-type cholinergic neurotrophic activity in both types of cells. NGF produced by astrocytes and fibroblasts that are activated by cytokines is likely to be important for development and regeneration of NGF-sensitive neurons in the central and peripheral nervous systems. FAU - Yoshida, K AU - Yoshida K AD - Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92193. FAU - Kakihana, M AU - Kakihana M FAU - Chen, L S AU - Chen LS FAU - Ong, M AU - Ong M FAU - Baird, A AU - Baird A FAU - Gage, F H AU - Gage FH LA - eng GR - AG06088/AG/NIA NIH HHS/United States GR - AG08514/AG/NIA NIH HHS/United States GR - NS28121/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Culture Media) RN - 0 (Cytokines) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Animals MH - Astrocytes/*metabolism MH - Cerebral Cortex/cytology/metabolism MH - Culture Media MH - Cytokines/*physiology MH - Cytological Techniques MH - Fibroblast Growth Factor 2/metabolism MH - Fibroblasts/metabolism MH - Nerve Growth Factors/metabolism/*physiology MH - Nerve Tissue Proteins/*biosynthesis MH - Neurons/drug effects/metabolism MH - Parasympathetic Nervous System/cytology/*metabolism MH - Septum Pellucidum/cytology/metabolism MH - Skin/cytology/*metabolism MH - gamma-Aminobutyric Acid/metabolism EDAT- 1992/09/01 00:00 MHDA- 1992/09/01 00:01 CRDT- 1992/09/01 00:00 PHST- 1992/09/01 00:00 [pubmed] PHST- 1992/09/01 00:01 [medline] PHST- 1992/09/01 00:00 [entrez] AID - 10.1111/j.1471-4159.1992.tb08331.x [doi] PST - ppublish SO - J Neurochem. 1992 Sep;59(3):919-31. doi: 10.1111/j.1471-4159.1992.tb08331.x.