Interleukin 1 and Tumor Necrosis Factor‐α Stimulate the Production of Colony‐Stimulating Factor 1 by Murine Astrocytes

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Abstract
Astrocytes have the ability to secrete colony‐stimulating factor 1 (CSF‐1), a growth factor known to stimulate the proliferation of brain macrophages. We have studied the effect of cytokines such as interleukin 1 (IL‐1), tumor necrosis factor‐α (TNFα), and interleukin 6 (IL‐6) on the production of CSF‐1 by cultured primary astrocytes and an astrocytic cell line derived from embryonic mouse brain. We observed that both TNFα and IL‐1 increased CSF‐1 mRNA and protein levels in the astrocytic cultures. In contrast, IL‐6 was ineffective. The CSF‐1 mRNA levels were strongly reduced by incubating immortalized astrocytic cells with staurosporine, a protein kinase C inhibitor, both in the absence and in the presence of cytokines. Conversely, 12‐O‐tetradecanoylphorbol 13‐acetate, a protein kinase C activator, increased CSF‐1 mRNA levels. These results suggest a mechanism whereby mononuclear phagocytes could favor their own recruitment in the CNS by producing cytokines.