Duration of expression of inducible nitric oxide synthase in glial cells.

Lipopolysaccharide (LPS) or a combination of interleukin (IL)-1 beta and interferon (IFN)-gamma cause transcriptional induction of a calcium-independent nitric oxide synthase (NOS) in astrocytes and C6 glioma cells. LPS induction of NOS in C6 cells was evidenced by a small amount of nitrite accumulation as compared with cells exposed to IL-1 beta/IFN-gamma, but the maximal NOS activity achieved (as revealed by cGMP formation) was the same. The NOS activity induced by LPS in C6 cells was maximal at 4 to 8 hr and then rapidly decreased, while NOS activity induced by IL-1 beta/IFN-gamma slowly decreased after 4 hr. In addition, the effects of re-presenting IL-1 beta/IFN-gamma to both astrocytes and C6 cells after maximal induction of activity of the inducible form of NOS were studied. The re-addition of cytokines prolonged both NOS mRNA expression and also enzyme activity, suggesting effects at either the transcriptional (further induction) or translational level (mRNA stability). These results imply that the time course of NO production by induced astrocytes depends both upon the nature of the inducing stimulus and the frequency of the cells' exposure to it.