Glucocorticoid regulation of eicosanoid production by glial cells under basal and stimulated conditions.
We measured the production of two eicosanoids, prostaglandin E2 and thromboxane-B2, by rat glial cell cultures under basal conditions, following stimulation with phorbol-12-myristate-13-acetate and the bacterial endotoxin lipopolysaccharide, and following treatment with synthetic glucocorticoids. Stimulation of rat glial cells in culture with either phorbol-12-myristate-13-acetate or lipopolysaccharide caused a 1.5-5.0-fold increase in prostaglandin E2 production, but did not affect thromboxane production. Pretreatment of the cultures with dexamethasone markedly inhibited the stimulated production of prostaglandin E2 but had only a modest effect on basal production. Dexamethasone did not affect the activity of the enzyme protein kinase C, a putative regulator of eicosanoid synthesis. Our findings show that glucocorticoids have the potential to modulate central nervous system eicosanoid production particularly under conditions of stimulated production, such as inflammatory and demyelinating disorders. This mechanism may explain, at least in part, the therapeutic benefit of glucocorticoids in patients with multiple sclerosis.
Brenner
T
T
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Boneh
A
A
Shohami
E
E
Abramsky
O
O
Weidenfeld
J
J
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D005938:Glucocorticoids / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D013929:Thromboxane B2; D003907:Dexamethasone; D011493:Protein Kinase C; D010741:Phospholipases A; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate