MODULATION OF INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION IN ASTROGLIAL CELLS

Nitric oxide is produced in the CNS by both constitutive and inducible isoforms of nitric oxide synthase. Once nitric oxide synthase is transcriptionally induced in astrocytes in vitro, these cells release large amounts of nitric oxide tonically. Glial cell-derived nitric oxide can be toxic to neurons and oligodendrocytes and is implicated in a variety of neuropathologies, suggesting that the expression of nitric oxide synthase in glia must be finely regulated. From northern and western blot analysis we have identified various agents (transforming growth factor-beta, nitric oxide, receptor agonists) that modulate cytokine-induced expression of nitric oxide synthase mRNA in astrocytes. This suggests that the magnitude and duration of nitric oxide production from activated astrocytes in vivo may be determined by signals from adjacent neurons and microglial cells.