CSF-1 expression is upregulated in astrocyte cultures by IL-1 and TNF and affects microglial proliferation and morphology in organotypic cultures

Astrocytes produce factors that control the growth and differentiation of many cell types within the CNS as well as play a role in the generation of the immune response. The extent to which these two functions interact has received less attention. We now report that astrocyte cultures established from rat brain endogenously express mRNA and low levels of secreted biologically active protein for the monocyte growth and differentiation factor colony stimulating factor-1 (CSF-1). Exposure of astrocytes to interleukin-1 (IL-1) and/or tumor necrosis factor (TNF) upregulated the expression of CSF-1 mRNA and protein. Following treatment with 100 U/ml of TNF, IL-1, or TNF+IL-1, maximum CSF-1 mRNA expression was observed at 3 hr. In the presence of IL-1 an increase in biologically active CSF-1 was detected in the astrocyte conditioned medium at 6 hr. These data indicate that the expression of CSF-1 by astrocytes can be modulated by exposure to the cytokines IL-1 and TNF. To determine whether CSF-1 provides a mitogenic signal for microglia during development, mouse spinal cord organotypic cultures were exposed to recombinant mouse CSF-1 (rmCSF-1), resulting in proliferation of microglia by 7 days and an increase in the number of ramified microglia over ameboid microglia by 14 days.