Prolactin induction of nitric oxide synthase in rat C6 glioma cells.
We have examined the neuroimmunoregulatory function of prolactin (PRL) on astrocytic inducible nitric oxide synthase (iNOS) expression in the C6 glioma cell line. After 24 h of PRL (5-100 nM) stimulation, a concentration-dependent increase of NO release, evaluated as nitrite, was observed in C6 culture medium. Moreover, both NO release and iNOS expression induced by interferon-gamma (250 U/ml) were enhanced by PRL (18-100 nM). PRL-induced NO release was inhibited by dexamethasone, an inhibitor of de novo iNOS synthesis. We used erbstatin (5 microg/ml), a potent inhibitor of protein tyrosine kinases, to test whether these proteins were required for signaling events evoked by PRL in these cells. This inhibitor was able to inhibit completely the PRL-induced NO production and iNOS expression. In conclusion, we provide evidence that NO production in glial cells can be regulated not only by cytokines but also by neuroimmunoregulatory hormones such as PRL, which is present in normal brain but may be elevated in several pathological states.
Raso
G M
GM
Department of Experimental Pharmacology, University of Naples Frederico II, Italy.
Meli
R
R
Gualillo
O
O
Pacilio
M
M
Di Carlo
R
R
D000818:Animals; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma / Q000473:pathology; D006873:Hydroquinones / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011388:Prolactin / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D009569:Nitric Oxide; D003907:Dexamethasone; D007371:Interferon-gamma; D011388:Prolactin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C048212:erbstatin