Phosphatidylinositol 3-kinase regulates proliferation of RAW 264.7 macrophages

Phosphatidylinositol 3-kinase (PI3-kinase) is an enzyme that acts as a dire ct biochemical link between a novel phosphatidylinositol pathway and a numb er of proteins containing intrinsic or associated kinase activities. Here w e demonstrate that wortmannin, PI3-kinase inhibitor, decreases the prolifer ation of RAW 264.7 macrophages and that another structurally unrelated inhi bitor of PI3-kinase. LY294002, also inhibits the proliferation. These resul ts indicate a possible involvement of PI3-kinase in RAW 264.7 macrophages g rowth regulation. Wortmannin stimulation of RAW 264.7 macrophages is follow ed 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 inhibitio n of cell proliferation a after 12 h of treatment. In addition, wortmannin or LY294002 inhibited the phorbol 12-myristate 13-acetate-induced macrophag es proliferation potently. These results suggest that PI3-kinase plays an i mportant role in growth regulation of RAW 264.7 macrophages and that protei n kinase C is a down stream effector of PI3-kinase.