Prolactin induction of nitric oxide synthase in rat C6 glioma cells

We have examined the neuroimmunoregulatory function of prolactin (PRL) on a strocytic inducible nitric oxide synthase (iNOS) expression in the C6 gliom a cell line. After 24 h of PRL (5-100 nnn) stimulation, a concentration-dep endent increase of NO release, evaluated as nitrite, was observed in C6 cul ture medium. Moreover, both NO release and iNOS expression induced by inter feron-gamma (250 U/ml) were enhanced by PRL (18-100 nM). PRL-induced NO rel ease was inhibited by dexamethasone, an inhibitor of de novo iNOS synthesis . We used erbstatin (5 mu g/ml), a potent inhibitor of protein tyrosine kin ases, to test whether these proteins were required for signaling events evo ked by PRL in these cells. This inhibitor was able to inhibit completely th e PRL-induced NO production and iNOS expression. In conclusion, we provide evidence that NO production in glial cells can be regulated not only by cyt okines but also by neuroimmunoregulatory hormones such as PRL, which is pre sent in normal brain but may be elevated in several pathological states.