Regulation of astrocyte proliferation by prostaglandin E2 and the alpha subtype of protein kinase C.
We found that astrocytes expressed the alpha subtype of protein kinase C. Treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) caused cultured astrocytes to proliferate. This effect of TPA was blocked by staurosporine, a potent protein kinase C inhibitor, suggesting the involvement of protein kinase C in astrocyte proliferation. Indomethacin, an inhibitor of prostaglandin formation, enhanced both the normal and TPA-induced proliferation of astrocytes. Authentic prostaglandin E2 blocked this effect of indomethacin and also partially blocked the effect of TPA, suggesting that the intracellular mechanisms involved in prostaglandin E2-regulated astrocyte growth might differ from those acting in protein kinase-dependent growth. The effect of prostaglandin E2 was blocked by a specific anti-prostaglandin E2 polyclonal antibody. Cultured astrocytes and microglia produced and released prostaglandin E2 in response to stimulants such as lipopolysaccharide, TPA, and lymphokines. Since the sensitivity of astrocytes and microglia to these stimuli was different, prostaglandin E2 may differentially regulate astrocyte proliferation under different physiological conditions, acting in an autocrine fashion for astrocytes and in a paracrine fashion for microglia.
Sawada
M
M
Division of Cell Biology, School of Medicine, Fujita Health University, Aichi, Japan.
Suzumura
A
A
Ohno
K
K
Marunouchi
T
T
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004789:Enzyme Activation; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000470:Alkaloids; D008070:Lipopolysaccharides; D011493:Protein Kinase C; D019311:Staurosporine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin