Regulation of astrocyte proliferation by prostaglandin E(2) and the α subtype of protein kinase C

We found that astrocytes expressed the α subtype of protein kinase C. Treatment with12-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 E(2) blocked this effect of indomethacin and also partially blocked the effect of TPA, suggesting that the intracellular mechanisms involved in prostaglandin E(2)-regulated astrocyte growth might differ from those acting in protein kinase-dependent growth. The effect of prostaglandin E(2) was blocked by a specific anti-prostaglandin E(2) polyclonal antibody. Cultured astrocytes and microglia produced and released prostaglandin E(2) in response to stimulants such as lipopolysaccharide, TPA, and lymphokines. Since the sensitivity of astrocytes and microglia to these stimuli was different, prostaglandin E(2) may differentially regulate astrocyte proliferation under different physiological conditions, acting in an autocrine fashion for astrocytes and in a paracrine fashion for microglia.