MODULATION BY TUMOR-NECROSIS-FACTOR-ALPHA OF HUMAN ASTROGLIAL CELL PRODUCTION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) AND GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF)

Phagocyte survival and function are enhanced by GM-CSF and G-CSF. The production of both CSFs can be induced in mesenchymal cells by tumor necrosis factor-alpha (TNF-alpha) and interleukin-I (IL-1). We have recently demonstrated that IL-1-alpha and beta-induced the production of GM-CSF and G-CSF by two human astroglial cell lines. In the present study, we examined the effects of TNF-alpha on the production of GM-CSF and G-CSF by U87MG, a human astroglial cell line that constitutively expresses GM-CSF and G-CSF, and U373MG, a second human astroglial cell line that does not produce CSF. We demonstrate that U87MG can be induced to increase its production of GM-CSF and G-CSF by exposure to TNF-alpha while U373MG is induced to produce GM-CSF but not G-CSF. These responses, measured by accumulation of elevated levels of CSF protein and mRNA, are rapid and sensitive. The implications of these findings to the immunopathogenesis of central nervous system infections are discussed.