Phosphatidylinositol 3-kinase regulates proliferation of RAW 264.7 macrophages

Phosphatidylinositol 3-kinase (P13-kinase) is an enzyme that acts as a direct biochemical link between a novel phosphatidylinositol pathway and a number of proteins containing intrinsic or associated kinase activities. Here we demonstrate that wortmannin, P13-kinase inhibitor, decreases the proliferation of RAW 264.7 macrophages and that another structurally unrelated inhibitor of P13-kinase, LY294002. also inhibits the proliferation. These results indicate a possible involvement of P13-kinase in RAW 264.7 macrophages growth regulation. Wortmannin stimulation of RAW 264.7 macrophages is followed by sustained expression of the mRNA of c-fos and a transient expression of the mRNA of c-jun. We also show that the wortmannin and LY294002 induce a cell cycle arrest in asynchronously growing cells leading to an inhibition of cell proliferation after 12 h of treatment. In addition, wortmannin or LY294002 inhibited the phorbol 12-myristate 13-acetate-induced macrophages proliferation potently. These results suggest that P13-kinase plays an important role in growth regulation of RAW 264.7 macrophages and that protein kinase C is a down stream effector of P13-kinase.