Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts

Kazunari Yoshida, M. Kakihana, L. S. Chen, M. Ong, A. Baird, F. H. Gage

研究成果: Article

69 引用 (Scopus)

抄録

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-1β (IL-1β), tumor necrosis factor-α (TNFα), and transforming growth factor-β1. 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-1β and TNFα 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-1β and TNFα 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.

元の言語English
ページ(範囲)919-931
ページ数13
ジャーナルJournal of Neurochemistry
59
発行部数3
出版物ステータスPublished - 1992
外部発表Yes

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Nerve Growth Factor
Fibroblasts
Astrocytes
Cholinergic Agents
Conditioned Culture Medium
Cytokines
Neurons
Interleukin-1
Fibroblast Growth Factor 1
Glutamate Decarboxylase
Choline O-Acetyltransferase
Tumor Necrosis Factor-alpha
Cytarabine
Serum-Free Culture Media
Bioactivity
GABAergic Neurons
Cholinergic Neurons
Peripheral Nervous System
Neurology
Transforming Growth Factors

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

これを引用

Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts. / Yoshida, Kazunari; Kakihana, M.; Chen, L. S.; Ong, M.; Baird, A.; Gage, F. H.

:: Journal of Neurochemistry, 巻 59, 番号 3, 1992, p. 919-931.

研究成果: Article

Yoshida, Kazunari ; Kakihana, M. ; Chen, L. S. ; Ong, M. ; Baird, A. ; Gage, F. H. / Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts. :: Journal of Neurochemistry. 1992 ; 巻 59, 番号 3. pp. 919-931.
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T1 - Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts

AU - Yoshida, Kazunari

AU - Kakihana, M.

AU - Chen, L. S.

AU - Ong, M.

AU - Baird, A.

AU - Gage, F. H.

PY - 1992

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N2 - 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-1β (IL-1β), tumor necrosis factor-α (TNFα), and transforming growth factor-β1. 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-1β and TNFα 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-1β and TNFα 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.

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-1β (IL-1β), tumor necrosis factor-α (TNFα), and transforming growth factor-β1. 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-1β and TNFα 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-1β and TNFα 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.

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KW - Choline acetyltransferase

KW - Cytokines

KW - Fibroblasts

KW - Nerve growth factor

KW - Neurotrophic activity

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