Interleukin 1 and tumor necrosis factor-alpha stimulate the production of colony-stimulating factor 1 by murine...

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-alpha (TNF alpha), 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 TNF alpha 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.